Mannanase Variants and Polynucleotides Encoding Same

ABSTRACT

The present invention relates to mannanase variants. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

REFERENCE TO A SEQUENCE LISTING

This application contains a Sequence Listing in computer readable form,which is incorporated herein by reference.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates to mannanase variants exhibiting mannanaseactivity, compositions comprising the mannanase variants,polynucleotides encoding the variants, methods of producing thevariants, and methods of using the variants.

Description of the Related Art

Endo-1,4-mannanases (EC 3.2.1.78) are involved in the random hydrolysisof (1→4)-β-D-mannosidic linkages in mannans, galactomannans,glucomannans and galactoglucomannans (Ademark et al. (1998) J.Biotechnol. 63:199-210).

Mannan containing polysaccharides are often a major component of thehemicellulose fraction in woods, both softwood and hardwood.

Essentially unsubstituted linear beta-1,4-mannan is found in fruits ofseveral palm trees, such as palm kernels and coconuts. Unsubstitutedbeta-1,4-mannan which is present e.g. in ivory nuts resembles cellulosein the conformation of the individual polysaccharide chains, and iswater-insoluble. In leguminous seeds, water-soluble galactomannan is themain storage carbohydrate comprising up to 20% of the total dry weight.See Moreira et al., (2008) Appl. Microbiol. Biotechnol. 79:165-178.Galactomannans have a linear beta-1,4-mannan backbone substituted withsingle alpha-1,6-galactose, optionally substituted with acetyl groups.Glucomannans are linear polysaccharides with a backbone ofbeta-1,4-linked mannose and glucose alternating in a more or lessregular manner, the backbone optionally being substituted with galactoseand/or acetyl groups. Mannans, galactomannans, glucomannans andgalactoglucomannans (i.e. glucomannan backbones with branched galactose)contribute to more than 50% of the softwood hemicellulose. Moreover, thecellulose of many red algae contains a significant amount of mannose.

Mannanases have been identified in several Bacillus organisms, but alsofrom other bacteria, fungi, plants, and animals. See, Araujo A. et al.,(1990) I. App. Bacteriol. 68:253-261; Dutta S. et al., (1997) PlantPhysiol. 113: 155-161; Puchar V. et al, (2004) Biochim. Biophys. Acta1674:239-250. Genes encoding these enzymes from a number of organismshave also been cloned and sequenced, many if not all have beenclassified also as members of glycosyl hydrolase (GH) family 5 or 26,based on their sequences. See, e.g., Bewley D. J., (1997) Planta203:454-459; Halstead J. R. et al., (2000) FEMS Microl. Lett. 192:197-203; Xu B. et al., (2002) Eur. J. Biochem. 269: 1753-1760;Henrissat, B. (1991) Biochem. J. 280:309-316.

Beta-mannanases have been used in commercial applications in, forexample, industries such as the paper and pulp industry, foodstuff andfeed industry, pharmaceutical industry and energy industry. Lee J. T.,et al., (2003) Poult. Sci. 82: 1925-1931; McCutchen M. C., et al.,(1996) Biotechnol. Bioeng. 52:332-339; Suurnakki A., et al., (1997) Adv.Biochem. Eng. Biotechnol, 57:261-287.

Within the household care industry, it has been known to use mannanasesin e.g. laundry detergents. In WO 1999/064619 an alkaline mannanase,which exhibites mannanase activity also in the alkaline pH range whenapplied in cleaning compositions, is disclosed.

In WO 2016/054176 other mannanases exhibiting beta-mannanase activityare disclosed.

However, mannanases with improved stability, in particular when used indetergents, have not been disclosed in the prior art. As can be seenfrom the data herein disclosed, the stability of a wild-type mannanasecan be significantly improved by protein engineering. Viewed from acommercial side, providing a mannanase having an improved stability,will have a great impact for the detergent producing industry.

Thus, it is the object of the present invention to provide mannanasevariants with improved stability compared to its parent.

SUMMARY OF THE INVENTION

The present invention relates to an isolated mannanase variant, whereinsaid variant comprises at least two substitutions, wherein (a) saidfirst substitution is in an amino acid position selected from thepositions 260, 288, 294, or 295, and (b) said at least secondsubstitution is selected from any other position in said variant,wherein numbering is according to SEQ ID NO: 2, said variant hasmannanase activity and has at least 58%, e.g. at least 60%, e.g., atleast 62%, at least 63%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 95%, at least 96%, atleast 97%, at least 98%, or at least 99%, but less than 100% sequenceidentity to the mature polypeptide of SEQ ID NO: 1 or the polypeptide ofSEQ ID NO: 2.

The present invention also relates to a composition comprising a variantas herein disclosed, use of such a composition in a domestic orindustrial cleaning process, an isolatedpolynucleotide encoding thevariants; nucleic acid constructs, vectors, and host cells comprisingthe polynucleotides; and methods of producing the variants as well asmethods of dishwashing or laundering in automatic machines using acomposition herein disclosed.

Definitions

Before the invention is described in further details, it is to beunderstood that the present variants, compositions and methods are notlimited to particular embodiments described, as such may, of course,differ. It is also to be understood that the terminology used herein isfor the purpose of describing particular embodiments only, and is notintended to be limiting, since the scope of the present invention willbe limited only by the appended claims.

Thus, prior to discussing the invention in further detail, the followingterms will first be defined. In accordance with the detaileddescription, the following abbreviations and definitions apply. Notethat the singular forms “a”, “an”, and “the” include plural referentsunless the context clearly dictates otherwise. Thus, for example,reference to “an enzyme” includes a plurality of such enzymes, andreference to “the dosage” includes reference to one or more dosages andequivalents thereof known to those skilled in the art, and so forth.

Certain ranges are presented herein with numerical values being precededby the term “about”. The term “about” as used herein, is to provideliteral support for the exact number that it precedes, as well as anumber that is near to or approximately the number that the termprecedes. In determining whether a number is near to or approximately aspecifically recited number, the near or approximating unrecited numbermay be a number which, in the context in which it is presented, providesthe substantial equivalent of the specifically recited number. Forexample, in connection with a numerical value, the term “about” refersto a range of −10% to +10% of the numerical value, unless term isotherwise specifically defined in context. In another example, thephrase a “pH value of about 9” refers to pH values of from 8.1 to 9.9,unless the pH value is specifically defined otherwise.

Mannanase: The term “mannanase” or “galactomannanase” as used hereinrefers to a mannanase enzyme defined as the officially named mannanendo-1,4-beta-mannosidase and having the alternative namesbeta-mannanase and endo-1,4-mannanase. The mannanase term also means apolypeptide or polypeptide domain of an enzyme that has the ability tocatalyze the cleavage or hydrolysis of (1→4) beta-D-mannosidic linkagesof mannans, galactomannans, glucomannans, and galactoglucomannans. Thus,it means that the mannanase has mannanase activity (EC 3.2.1.78). Forpurposes of the present invention, mannanase activity is determinedaccording to the procedure described in the Examples. In one aspect, thevariants of the present invention have at least 20%, e.g., at least 40%,at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, atleast 95%, or at least 100% of the mannanase activity of the maturepolypeptide of SEQ ID NO: 1.

Allelic variant: The term “allelic variant” means any of two or morealternative forms of a gene occupying the same chromosomal locus.Allelic variation arises naturally through mutation, and may result inpolymorphism within populations. Gene mutations can be silent (no changein the encoded polypeptide) or may encode polypeptides having alteredamino acid sequences. An allelic variant of a polypeptide is apolypeptide encoded by an allelic variant of a gene.

cDNA: The term “cDNA” means a DNA molecule that can be prepared byreverse transcription from a mature, spliced, mRNA molecule obtainedfrom a eukaryotic or prokaryotic cell. cDNA lacks intron sequences thatmay be present in the corresponding genomic DNA. The initial, primaryRNA transcript is a precursor to mRNA that is processed through a seriesof steps, including splicing, before appearing as mature spliced mRNA.

Coding sequence: The term “coding sequence” means a polynucleotide,which directly specifies the amino acid sequence of a variant. Theboundaries of the coding sequence are generally determined by an openreading frame, which begins with a start codon such as ATG, GTG or TTGand ends with a stop codon such as TAA, TAG, or TGA. The coding sequencemay be a genomic DNA, cDNA, synthetic DNA, or a combination thereof.

Control sequences: The term “control sequences” means nucleic acidsequences necessary for expression of a polynucleotide encoding avariant of the present invention. Each control sequence may be native(i.e., from the same gene) or foreign (i.e., from a different gene) tothe polynucleotide encoding the variant or native or foreign to eachother. Such control sequences include, but are not limited to, a leader,polyadenylation sequence, propeptide sequence, promoter, signal peptidesequence, and transcription terminator. At a minimum, the controlsequences include a promoter, and transcriptional and translational stopsignals. The control sequences may be provided with linkers for thepurpose of introducing specific restriction sites facilitating ligationof the control sequences with the coding region of the polynucleotideencoding a variant.

Comprising: The term “comprising” as used herein refers to, including,but not limited to, the component(s) or feature(s) after the term“comprising”. The component(s) or feature(s) after the term “comprising”are required or mandatory, but the embodiment, may further include othernon-mandatory or optional component(s) or feature(s).

Consisting of: The term “consisting of” as used herein refers to,including, and limited to, the component(s) or feature(s) after the term“consisting of”. The component(s) or feature(s) after the term“consisting of” are therefore required or mandatory, and no othernon-mandatory or optional component(s) or feature(s) are present in theembodiments.

Expression: The term “expression” includes any step involved in theproduction of a variant including, but not limited to, transcription,post-transcriptional modification, translation, post-translationalmodification, and secretion.

Expression vector: The term “expression vector” as used herein, refersto a linear or circular DNA molecule that comprises a polynucleotideencoding a variant and is operably linked to control sequences thatprovide for its expression. Such control sequences may include apromotor to affect transcription, an optional operator sequence tocontrol transcription, a sequence encoding suitable ribosome-bindingsites on the mRNA, and sequence which control termination oftranscription and translation. Different cell types may be used withdifferent expression vectors.

Fragment: The term “fragment” means a polypeptide having one or more(e.g., several) amino acids absent from the amino and/or carboxylterminus of a mature polypeptide; wherein the fragment has mannanaseactivity. In one aspect, a fragment contains at least 250 amino acidresidues (e.g., amino acids 250 to 300 of SEQ ID NO: 2), at least 260amino acid residues (e.g., amino acids 260 to 300 of SEQ ID NO: 2), atleast 270 amino acid residues (e.g., amino acids 270 to 300 of SEQ IDNO: 2), or at least 285 amino acid residues (e.g., amino acids 285 to300 of SEQ ID NO: 2.

Host cell: The term “host cell” means any cell type that is susceptibleto transformation, transfection, transduction, or the like with anucleic acid construct or expression vector comprising a polynucleotideof the present invention. The term “host cell” encompasses any progenyof a parent cell that is not identical to the parent cell due tomutations that occur during replication. Host cells useful in thepresent invention are generally prokaryotic or eukaryotic host,including any transformable microorganism in which expression can beachieved. Host cells are transformed or transfected with vectorsconstructed using recombinant DNA techniques. Such transformed hostcells may be capable of one or both of replicating the vectors encodingthe variant of the present invention and expressing the desired peptideproduct.

Improved property: The term “improved property” as used herein, refersto a characteristic associated with a variant that is improved comparedto the parent. Such improved properties include, but are not limited to,catalytic efficiency, catalytic rate, in-detergent stability, chemicalstability, oxidation stability, pH activity, pH stability, specificactivity, stability under storage conditions, substrate binding,substrate cleavage, substrate specificity, substrate stability, surfaceproperties, thermal activity, and thermostability.

In-detergent stability: The term “in-detergent stability” as usedherein, refers to the stability of a mannanase enzyme, being both awild-type, parent or variant, when it has been incubated in a detergent.For the purposes of the present invention, in-detergent stability may bedetermined as shown in Example 3.

Isolated: The term “isolated” as used herein, refers to a substance in aform or environment which does not occur in nature. Non-limitingexamples of isolated substances include (1) any non-naturally occurringsubstance, (2) any substance including, but not limited to, any enzyme,variant, nucleic acid, protein, peptide or cofactor, that is at leastpartially removed from one or more or all of the naturally occurringconstituents with which it is associated in nature; (3) any substancemodified by the hand of man relative to that substance found in nature;or (4) any substance modified by increasing the amount of the substancerelative to other components with which it is naturally associated(e.g., multiple copies of a gene encoding the substance; use of astronger promoter than the promoter naturally associated with the geneencoding the substance). An isolated substance may be present in afermentation broth sample.

Mature polypeptide: The term “mature polypeptide” as used herein, refersto a polypeptide in its final form following translation and anypost-translational modifications, such as N-terminal processing,C-terminal truncation, glycosylation, phosphorylation, etc. In oneaspect, the mature polypeptide is amino acids 1 to 298 of SEQ ID NO: 1based on the SignalP 3.0 predictions (Using neural networks (NN) andhidden Markov models (HMM) trained on Gram-positive bacteria) thatpredicts amino acids −28 to −1 of SEQ ID NO: 1 are a signal peptide. Itis known in the art that a host cell may produce a mixture of two ofmore different mature polypeptides (i.e., with a different C-terminaland/or N-terminal amino acid) expressed by the same polynucleotide.

Mature polypeptide coding sequence: The term “mature polypeptide codingsequence” as used herein, refers to a polynucleotide that encodes amature polypeptide having mannanase activity. In one aspect, the maturepolypeptide coding sequence is nucleotides 218 to 1111 of SEQ ID NO: 3.

Mutant: The term “mutant” as used herein, refers to a polynucleotideencoding a variant.

Nucleic acid construct: The term “nucleic acid construct” as usedherein, refers to a nucleic acid molecule, either single- ordouble-stranded, which is isolated from a naturally occurring gene or ismodified to contain segments of nucleic acids in a manner that would nototherwise exist in nature or which is synthetic, which comprises one ormore control sequences.

Operably linked: The term “operably linked” as used herein, refers to aconfiguration in which a control sequence is placed at an appropriateposition relative to the coding sequence of a polynucleotide such thatthe control sequence directs expression of the coding sequence. Thus,“operably linked” means that a regulatory region or functional domainhaving a known or desired activity, such as a promoter, terminator,signal sequence or enhancer region, is attached to or linked to a target(e.g., a gene or polypeptide) in such a manner as to allow theregulatory region or functional domain to control the expression,secretion or function of that target according to its known or desiredactivity.

Parent or parent mannanase: The term “parent”, “parent mannanase” or“parent polypeptide” as used herein refers to any polypeptide withmannanase activity to which a modification is made to produce the enzymevariants of the present invention. In the present invention, it is to beunderstood, that a parent polypeptide both refers to anaturally-occurring polypeptide that does not include a man-madesubstitution, insertion, or deletion at one or more amino acid positionsand to non-naturally-occurring polypeptides such as hybrids, orpolypeptides comprising man-made modifications. Similarly, the term“parent” with respect to a polynucleotide, refers to both anaturally-occurring polynucleotide that does not include a man-madenucleoside change and to non-naturally-occurring polynucleotides such ashybrids, or polynucleotides comprising man-made modifications.Apolynucleotide encoding a parent polypeptide is not limited to anaturally-occurring polynucleotide, but rather encompasses anypolynucleotide encoding the parent polypeptide. The parent mannanase maybe any mannanase having at least 58%, 60%, such as at least 62%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90%, at least 95%, or 100% sequence identity to SEQ ID NO: 1 or 2.In one particular aspect of the present invention, the parent mannanaseis the polypeptide of SEQ ID NO: 2 or a polypeptide having at least 58%sequence identity to SEQ ID NO: 2.

Polypeptide or enzyme: The terms “polypeptide” and “enzyme” may be usedinterchangeably to refer to polymers of any length comprising amino acidresidues linked by peptide bonds. The conventional one-letter orthree-letter codes for amino acid residues are used herein. The polymermay be linear or branched, it may comprise modified amino acids, and itmay be interrupted by non-amino acids. The terms also encompass an aminoacid polymer that has been modified naturally or by intervention; forexample, disulfide bond formation, glycosylation, lipidation,acetylation, phosphorylation, or any other manipulation or modification,such as conjugation with a labeling component. Also included within thedefinition are, for example, polypeptides containing one or more analogsof an amino acid (including, for example, unnatural amino acids, etc.)as well as other modifcations known in the art.

Sequence identity: The relatedness between two amino acid sequences orbetween two nucleotide sequences is described by the parameter “sequenceidentity”. As used herein, “percent (%) sequence identity” with respectto the amino acid or nucleotide sequence identified herein is defined asthe percentage of amino acid residues or nucleotides in a candidatesequence that are identical with the amino acid residues or nucleotidesin a mannanase sequence as set out in the sequence of SEQ ID NO: 1 orthe sequence of SEQ ID NO: 2, or for nucleotides the sequence of SEQ IDNO: 3, after aligning the sequences and introducing gaps, if necessary,to achieve the maximum percent sequence identity, and not consideringany conservative substitutions as part of the sequence identity.

For purposes of the present invention, the sequence identity between twoamino acid sequences is determined using the Needleman-Wunsch algorithm(Needleman and Wunsch, 1970, J. Mol. Biol. 48: 443-453) as implementedin the Needle program of the EMBOSS package (EMBOSS: The EuropeanMolecular Biology Open Software Suite, Rice et al., 2000, Trends Genet.16: 276-277), preferably version 5.0.0 or later. The parameters used aregap open penalty of 10, gap extension penalty of 0.5, and the EBLOSUM62(EMBOSS version of BLOSUM62) substitution matrix. The output of Needlelabeled “longest identity” (obtained using the -nobrief option) is usedas the percent identity and is calculated as follows:

(Identical Residues×100)/(Length of Alignment−Total Number of Gaps inAlignment)

For purposes of the present invention, the sequence identity between twodeoxyribonucleotide sequences is determined using the Needleman-Wunschalgorithm (Needleman and Wunsch, 1970, supra) as implemented in theNeedle program of the EMBOSS package (EMBOSS: The European MolecularBiology Open Software Suite, Rice et al., 2000, supra), preferablyversion 5.0.0 or later. The parameters used are gap open penalty of 10,gap extension penalty of 0.5, and the EDNAFULL (EMBOSS version of NCBINUC4.4) substitution matrix. The output of Needle labeled “longestidentity” (obtained using the -nobrief option) is used as the percentidentity and is calculated as follows:

(Identical Deoxyribonucleotides×100)/(Length of Alignment−Total Numberof Gaps in Alignment)

Variant: The term “variant” as used herein, refers to a polypeptidehaving mannanase activity comprising an modification, i.e., asubstitution or deletion, at one position. A substitution meansreplacement of the amino acid occupying a position with a differentamino acid; and a deletion means removal of the amino acid occupying aposition. The variants of the present invention have at least 20%, e.g.,at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, atleast 90%, at least 95%, or at least 100% of the mannanase activity ofthe mature polypeptide of SEQ ID NO: 1 or SEQ ID NO: 2.

Wild-type mannanase: The term “wild-type mannanase” as used herein,refers to a mannanase expressed by a naturally occurring microorganism,such as a bacterium, yeast, or filamentous fungus found in nature.

Sequences Referred to in the Invention

-   SEQ ID NO: 1 is a parent mannanase including the signal peptide.-   SEQ ID NO: 2 is the mature polypeptide of SEQ ID NO: 1.-   SEQ ID NO: 3 is a nucleotide sequence encoding the polypeptide of    SEQ ID NO: 1.-   SEQ ID NO: 4 is a mature protease.

Conventions for Designation of Variants

For purposes of the present invention, the mature polypeptide disclosedin SEQ ID NO: 2 is used to determine the corresponding amino acidresidue in another mannanase. The amino acid sequence of anothermannanase is aligned with the mature polypeptide disclosed in SEQ ID NO:2, and based on the alignment, the amino acid position numbercorresponding to any amino acid residue in the mature polypeptidedisclosed in SEQ ID NO: 2 is determined using the Needleman-Wunschalgorithm (Needleman and Wunsch, 1970, J. Mol. Biol. 48: 443-453) asimplemented in the Needle program of the EMBOSS package (EMBOSS: TheEuropean Molecular Biology Open Software Suite, Rice et al., 2000,Trends Genet. 16: 276-277), preferably version 5.0.0 or later. Theparameters used are gap open penalty of 10, gap extension penalty of0.5, and the EBLOSUM62 (EMBOSS version of BLOSUM62) substitution matrix.

Identification of the corresponding amino acid residue in anothermannanase can be determined by an alignment of multiple polypeptidesequences using several computer programs including, but not limited to,MUSCLE (multiple sequence comparison by log-expectation; version 3.5 orlater; Edgar, 2004, Nucleic Acids Research 32: 1792-1797), MAFFT(version 6.857 or later; Katoh and Kuma, 2002, Nucleic Acids Research30: 3059-3066; Katoh et al., 2005, Nucleic Acids Research 33: 511-518;Katoh and Toh, 2007, Bioinformatics 23: 372-374; Katoh et al., 2009,Methods in Molecular Biology 53709-64; Katoh and Toh, 2010,Bioinformatics 26:1899-1900), and EMBOSS EMMA employing ClustalW (1.83or later; Thompson et al., 1994, Nucleic Acids Research 22: 4673-4680),using their respective default parameters.

When the other enzyme has diverged from the mature polypeptide of SEQ IDNO: 2 such that traditional sequence-based comparison fails to detecttheir relationship (Lindahl and Elofsson, 2000, J. Mol. Biol. 295:613-615), other pairwise sequence comparison algorithms can be used.Greater sensitivity in sequence-based searching can be attained usingsearch programs that utilize probabilistic representations ofpolypeptide families (profiles) to search databases. For example, thePSI-BLAST program generates profiles through an iterative databasesearch process and is capable of detecting remote homologs (Atschul etal., 1997, Nucleic Acids Res. 25: 3389-3402). Even greater sensitivitycan be achieved if the family or superfamily for the polypeptide has oneor more representatives in the protein structure databases. Programssuch as GenTHREADER (Jones, 1999, J. Mol. Biol. 287: 797-815; McGuffinand Jones, 2003, Bioinformatics 19: 874-881) utilize information from avariety of sources (PSI-BLAST, secondary structure prediction,structural alignment profiles, and solvation potentials) as input to aneural network that predicts the structural fold for a query sequence.Similarly, the method of Gough et al., 2000, J. Mol. Biol. 313: 903-919,can be used to align a sequence of unknown structure with thesuperfamily models present in the SCOP database. These alignments can inturn be used to generate homology models for the polypeptide, and suchmodels can be assessed for accuracy using a variety of tools developedfor that purpose.

For proteins of known structure, several tools and resources areavailable for retrieving and generating structural alignments. Forexample the SCOP superfamilies of proteins have been structurallyaligned, and those alignments are accessible and downloadable. Two ormore protein structures can be aligned using a variety of algorithmssuch as the distance alignment matrix (Holm and Sander, 1998, Proteins33: 88-96) or combinatorial extension (Shindyalov and Bourne, 1998,Protein Engineering 11: 739-747), and implementation of these algorithmscan additionally be utilized to query structure databases with astructure of interest in order to discover possible structural homologs(e.g., Holm and Park, 2000, Bioinformatics 16: 566-567).

In describing the variants of the present invention, the nomenclaturedescribed below is adapted for ease of reference. The accepted IUPACsingle letter or three letter amino acid abbreviation is employed.

Substitutions. For an amino acid substitution, the followingnomenclature is used: Original amino acid, position, substituted aminoacid. Accordingly, the substitution of threonine at position 226 withalanine is designated as “Thr226Ala” or “T226A”. Multiple mutations areseparated by addition marks (“+”), e.g., “Gly205Arg+Ser411Phe” or“G205R+S411F”, representing substitutions at positions 205 and 411 ofglycine (G) with arginine (R) and serine (S) with phenylalanine (F),respectively.

Deletions. For an amino acid deletion, the following nomenclature isused: Original amino acid, position, *. Accordingly, the deletion ofglycine at position 195 is designated as “Glyl95*” or “G195*”. Multipledeletions are separated by addition marks (“+”), e.g., “Gly195*+Ser411*”or “G195*+S411*”.

Insertions. For an amino acid insertion, the following nomenclature isused: Original amino acid, position, original amino acid, inserted aminoacid. Accordingly the insertion of lysine after glycine at position 195is designated “Gly195GlyLys” or “G195GK”. An insertion of multiple aminoacids is designated [Original amino acid, position, original amino acid,inserted amino acid #1, inserted amino acid #2; etc.]. For example, theinsertion of lysine and alanine after glycine at position 195 isindicated as “Gly195GlyLysAla” or “G195GKA”.

In such cases the inserted amino acid residue(s) are numbered by theaddition of lower case letters to the position number of the amino acidresidue preceding the inserted amino acid residue(s). In the aboveexample. the sequence would thus be:

Parent: Variant: 195 195 195a 195b G G-K-A

Multiple modifications. Variants comprising multiple modifications areseparated by addition marks (“+”), e.g., “Arg170Tyr+Gly195Glu” or“R170Y+G195E” representing a substitution of arginine and glycine atpositions 170 and 195 with tyrosine and glutamic acid, respectively.

Different modifications. Where different modifications can be introducedat a position, the different modifications are separated by a comma,e.g., “Arg170Tyr,Glu” represents a substitution of arginine at position170 with tyrosine or glutamic acid. Thus, “Tyr167Gly,Ala+Arg170Gly,Ala”designates the following variants: “Tyr167Gly+Arg170Gly”,“Tyr167Gly+Arg170Ala”, “Tyr167Ala+Arg170Gly”, and “Tyr167Ala+Arg170Ala”.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to isolated mannanase variant comprises atleast two substitutions, wherein (a) said first substitution is in anamino acid position selected from the positions 260, 288, 294, or 295,and (b) said at least second substitution is selected from any otherposition in said variant, wherein numbering is according to SEQ ID NO:2, said variant has mannanase activity and has at least 58%, e.g. atleast 60%, e.g., at least 62%, at least 63%, at least 65%, at least 70%,at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, atleast 96%, at least 97%, at least 98%, or at least 99%, but less than100% sequence identity to the mature polypeptide of SEQ ID NO: 1 or thepolypeptide of SEQ ID NO: 2.

The inventors of the present invention has found that a modification inone of the above listed positions of (a) provides a mannanase variantswhich have an improved stability compared to the parent mannanase, i.e.a mannanase not comprising a modification in any one of the listedpositions. Thus, the improvement of the mannanase variants is observedwhen the variant has at least one of (a) listed positions. Whencombining (a) listed positions with any other modification, it has beenobserved that the stability is maintained. Thus, these positions arebelieved to be important for stability of mannanases. In particular, thestability may be observed as stability in detergent compositions. Suchdetergent stability may be determined as described in Example 3, i.e. byincubating the variants in detergent e.g. for 24hrs at 40° C. or for16hrs at 45° C., and then measureing the residual activity. The residualactivity is correlated/compared to the residual activity of a parentmannanase incubated at 4° C. for the equal amount of hours. Theimprovement of the mannanase variants are given as half-life improvementfactor (HIF).

Thus, the present invention provides variants of a parent mannanase,wherein the variant comprises at least one substitution in one or moreof the positions 260, 288, 294, and 295, wherein numbering is accordingto SEQ ID NO: 2, and at least one second (or further) substitution in aposition which is in any other position in the amino acid sequence. Theterm “second substitution” or “further substitution” as used herein, areto be understood as being a substitution which is not in any of thefollowing positions 260, 288, 294, and 295. However, the variantaccording to the invention may comprise more than one substitution inany one of the positions 260, 288, 294, and 295. Furthermore, the term“second substitution” is to be understood as “at least one secondsubstitution”, i.e. the second substitution may be in one or morepositions.

The stability in detergent compositions may herein be referred to a “indetergent stability” and falls under the definition elsewhere describedherein. The terms may be used interchangeably, but constitute the samemeaning and purpose for the present invention. The stability has beendetermined as described in the Examples.

As can be seen from the Examples, all the disclosed variants have animproved stability, in particular when tested under stress. Such stressin according to the present invention may be increased by altering (i.e.raising the pH), incubating for a longer/extended time period, altered(i.e raised) temperature and/or in the presence of a protease.

It is to be understood that the variants of the present inventioncomprises at least two modifications, such as substitutions, which meansthat the variants may comprise a substitution in one of the positionslisted in (a) and then the second/further substitution(s) is in anyother positions herein disclosed. However, it is also to be understoodthat variants of the present invention may be variants that comprise asubstitution in more than one of the listed positions in (a), i.e. intwo, three or all four positions. Thus, embodiments of the presentinvention encompass variants comprising or consisting of a substitutionin the following positions: 260+288, 260+294, 260+295, 288+294, 288+295,294+295, 260+288+294, 260+288+295, 260+294+295, 288+294+295, and260+288+294+295.

In one embodiment, the mannanase variant comprises a modification in thepositions corresponding to positions 260 and 288 of SEQ ID NO: 2, and asecond modification selected from any other position in said variant.

In one embodiment, the mannanase variant comprises a modification in thepositions corresponding to positions 260 and 294 of SEQ ID NO: 2, and asecond modification selected from any other position in said variant.

In one embodiment, the mannanase variant comprises a modification in thepositions corresponding to positions 260 and 295 of SEQ ID NO: 2, and asecond modification selected from any other position in said variant.

In one embodiment, the mannanase variant comprises a modification in thepositions corresponding to positions 288 and 294 of SEQ ID NO: 2, and asecond modification selected from any other position in said variant.

In one embodiment, the mannanase variant comprises a modification in thepositions corresponding to positions 288 and 295 of SEQ ID NO: 2, and asecond modification selected from any other position in said variant.

In one embodiment, the mannanase variant comprises a modification in thepositions corresponding to positions 294 and 295 of SEQ ID NO: 2, and asecond modification selected from any other position in said variant.

In one embodiment, the mannanase variant comprises a modification in thepositions corresponding to positions 260, 288, and 294 of SEQ ID NO: 2,and a second modification selected from any other position in saidvariant.

In one embodiment, the mannanase variant comprises a modification in thepositions corresponding to positions 260, 288, and 295 of SEQ ID NO: 2,and a second modification selected from any other position in saidvariant.

In one embodiment, the mannanase variant comprises a modification in thepositions corresponding to positions 260, 294, and 295 of SEQ ID NO: 2,and a second modification selected from any other position in saidvariant.

In one embodiment, the mannanase variant comprises a modification in thepositions corresponding to positions 288, 294, and 295 of SEQ ID NO: 2,and a second modification selected from any other position in saidvariant.

In one embodiment, the mannanase variant comprises a modification in thepositions corresponding to positions 260, 288, 294, and 295 of SEQ IDNO: 2, and a second modification selected from any other position insaid variant.

In one embodiment, the alteration is a substitution. In one embodiment,the substitution in the position corresponding to position 260 of SEQ IDNO: 2, is F, Y, L, or T, preferably F. In one embodiment, thesubstitution in the position corresponding to position 288 of SEQ ID NO:2, is I. In one embodiment, the substitution in the positioncorresponding to position 294 of SEQ ID NO: 2, is P, K, I, R, V, or H,preferably P. In one embodiment, the substitution in the positioncorresponding to position 295 of SEQ ID NO: 2, is K, V, P, L, R, A, N,M, or I, preferably P or V.

In one embodiment, the alteration is a deletion.

In an embodiment, the at least one second substitution is in at leastone or more positions selected from the positions: 1, 2, 3, 4, 5, 6, 8,11, 13, 14, 18, 30, 32, 33, 34, 35, 37, 41, 45, 47, 57, 59, 60, 63, 65,70, 71, 74, 77, 78, 80, 82, 83, 93, 95, 97, 98, 100, 104, 108, 111, 114,116, 118, 119, 131, 133, 135, 136, 139, 142, 143, 150, 169, 172, 174,176, 177, 180, 183, 184, 185, 196, 200, 202, 203, 205, 210, 213, 228,229, 234, 235, 241, 243, 244, 250, 254, 257, 262, 266, 268, 270, 272,273, 276, 279, 280, 283, 286, 290, 296, and 298, wherein numbering isaccording to SEQ ID NO: 2.

When the Improvement Factor (IF) is more than 1.0, it means that thevariant tested has an improved property, such as improved stability,compared to the parent mannanase.

The substitution may be made in any one of the positions correspondingto positions: 1, 2, 3, 5, 6, 8, 9, 10, 11, 13, 14, 16, 17, 18, 19, 21,35, 37, 38, 39, 41, 44, 45, 47, 59, 60, 62, 65, 67, 68, 70, 71, 74, 77,78, 79, 80, 81, 82, 83, 93, 95, 96, 97, 98, 100, 104, 107, 110, 111,114, 115, 116, 118, 119, 132, 133, 135, 136, 139, 142, 143, 147, 150,152, 154, 164, 167, 169, 174, 175, 176, 177, 180, 181, 183, 184, 185,199, 200, 202, 203, 205, 206, 210, 212, 213, 214, 215, 226, 229, 234,235, 241, 242, 243, 244, 254, 257, 258, 259, 260, 261, 267, 270, 273,276, 279, 280, 283, 285, 286, 288, 289, 290, 292, 293, 294, 295, 296,299, and 301, wherein numbering is according to SEQ ID NO: 2.

Unless specifically disclosed herein, the numbering of amino acidresidues or positions, are done according to SEQ ID NO: 2.

In one embodiment, the one or more positions are selected from thepositions 14, 37, 47, 77, 81, 82, 83, 93, 98, 116, 135, 136, 241, 242,257, and 258 of the polypeptide of SEQ ID NO: 2.

In particular, the mannanase variant comprises two modifications inpositions selected from the group of position sets: 14+260, 14+288,14+294, 14+295, 37+260, 37+288, 37+294, 37+295, 47+260, 47+288, 47+294,47+295, 77+260, 77+288, 77+294, 77+295, 81+260, 81+288, 81+294, 81+295,82+260, 82+288, 82+294, 82+295, 83+260, 83+288, 83+294, 83+295, 93+260,93+288, 93+294, 93+295, 98+260, 98+288, 98+294, 98+295, 116+260,116+288, 116+294, 116+295, 135+260, 135+288, 135+294, 135+295, 136+260,136+288, 136+294, 136+295, 241+260, 241+288, 241+294, 241+295, 242+260,242+288, 242+294, 242+295, 257+260, 257+288, 257+294, 257+295, 258+260,258+288, 258+294, 258+295, and 260+288, wherein numbering is accordingto SEQ ID NO: 2.

In one embodiment, the at least two substitutions are selected from thegroup of positions: 14+260, 14+288, 14+294, 14+295, 37+260, 37+288,37+294, 37+295, 47+260, 47+288, 47+294, 47+295, 77+260, 77+288, 77+294,77+295, 81+260, 81+288, 81+294, 81+295, 82+260, 82+288, 82+294, 82+295,83+260, 83+288, 83+294, 83+295, 93+260, 93+288, 93+294, 93+295, 98+260,98+288, 98+294, 98+295, 116+260, 116+288, 116+294, 116+295, 135+260,135+288, 135+294, 135+295, 136+260, 136+288, 136+294, 136+295, 241+260,241+288, 241+294, 241+295, 242+260, 242+288, 242+294, 242+295, 257+260,257+288, 257+294, 257+295, 258+260, 258+288, 258+294, 258+295, and260+288, wherein numbering is according to SEQ ID NO: 2.

In one embodiment, the at least second substitution is in one or both ofpositions 93 and 136 of the polypeptide of SEQ ID NO: 2.

Specifically, the invention relates to mannanase variants comprising asubstitution in the following group of positions: 14+93+260, 14+93+288,14+93+294, 14+93+295, 37+93+260, 37+93+288, 37+93+294, 37+93+295,47+93+260, 47+93+288, 47+93+294, 47+93+295, 77+93+260, 77+93+288,77+93+294, 77+93+295, 81+93+260, 81+93+288, 81+93+294, 81+93+295,82+93+260, 82+93+288, 82+93+294, 82+93+295, 83+93+260, 83+93+288,83+93+294, 83+93+295, 93+98+260, 93+98+288, 93+98+294, 93+98+295,93+116+260, 93+116+288, 93+116+294, 93+116+295, 93+135+260, 93+135+288,93+135+294, 93+135+295, 93+136+260, 93+136+288, 93+136+294, 93+136+295,93+241+260, 93+241+288, 93+241+294, 93+241+295, 93+242+260, 93+242+288,93+242+294, 93+242+295, 93+257+260, 93+257+288, 93+257+294, 93+257+295,93+258+260, 93+258+288, 93+258+294, 93+258+295, and 93+260+288, whereinnumbering is according to SEQ ID NO: 2.

In another embodiment, the invention relates to mannanase variantscomprising a substitution in the following group of positions:14+136+260, 14+136+288, 14+136+294, 14+136+295, 37+136+260, 37+136+288,37+136+294, 37+136+295, 47+136+260, 47+136+288, 47+136+294, 47+136+295,77+136+260, 77+136+288, 77+136+294, 77+136+295, 81+136+260, 81+136+288,81+136+294, 81+136+295, 82+136+260, 82+136+288, 82+136+294, 82+136+295,83+136+260, 83+136+288, 83+136+294, 83+136+295, 93+136+260, 93+136+288,93+136+294, 93+136+295, 98+136+260, 98+136+288, 98+136+294, 98+136+295,116+136+260, 116+136+288, 116+136+294, 116+136+295, 135+136+260,135+136+288, 135+136+294, 135+136+295, 136+241+260, 136+241+288,136+241+294, 136+241+295, 136+242+260, 136+242+288, 136+242+294,136+242+295, 136+257+260, 136+257+288, 136+257+294, 136+257+295,136+258+260, 136+258+288, 136+258+294, 136+258+295,and 136+260+288,wherein numbering is according to SEQ ID NO: 2.

In another embodiment, the invention relates to mannanase variantscomprising a substitution in the following group of positions:14+93+136+260, 14+93+136+288, 14+93+136+294, 14+93+136+295,37+93+136+260, 37+93+136+288, 37+93+136+294, 37+93+136+295,47+93+136+260, 47+93+136+288, 47+93+136+294, 47+93+136+295,77+93+136+260, 77+93+136+288, 77+93+136+294, 77+93+136+295,81+93+136+260, 81+93+136+288, 81+93+136+294, 81+93+136+295,82+93+136+260, 82+93+136+288, 82+93+136+294, 82+93+136+295,83+93+136+260, 83+93+136+288, 83+93+136+294, 83+93+136+295, 93+136+260,93+136+288, 93+136+294, 93+136+295, 93+98+136+260, 93+98+136+288,93+98+136+294, 93+98+136+295, 93+116+136+260, 93+116+136+288,93+116+136+294, 93+116+136+295, 93+135+136+260, 93+135+136+288,93+135+136+294, 93+135+136+295, 93+136+260, 93+136+288, 93+136+294,93+136+295, 93+136+241+260, 93+136+241+288, 93+136+241+294,93+136+241+295, 93+136+242+260, 93+136+242+288, 93+136+242+294,93+136+242+295, 93+136+257+260, 93+136+257+288, 93+136+257+294,93+136+257+295, 93+136+258+260, 93+136+258+288, 93+136+258+294,93+136+258+295, and 93+136+260+288, wherein numbering is according toSEQ ID NO: 2.

In one embodiment, the at least two substitutions are selected from A1G,A1V, N2E, S3P, G4D, F5H, Y6H, Y6M, Y6F, Y6W, Y6H, S8T, S8P, S8R, T11K,T11R, Y13F, D14S, D14K, N18V, N18R, A30T, Y32F, Y32W, K33Q, D34G, Q35L,T37P, E41V, E41N, N45G, G47S, G47A, D57N, G59Q, Q60R, K63R, K63Q, D65E,R70K, N71S, S74K, E77T, E77N, D78G, H80K, V82R, V82I, V82S, A83P, A83S,Y93Q, Y93A, S95D, A97R, S98P, S98D, N100Y, D104A, D104G, E108S, S111A,S111K, S111R, I114Q, I114M, I114W, K116R, D118K, T119R, S131T, E133R,E133Q, D135P, A136P, D139A, D139R, K142M, K142V, K142S, K142R, Q143R,N150T, N150R, N150S, Q169A, Q169R, Q169K, H172R, Y174R, Y174L, Y174W,Y174F, R176Q, E177S, E177Y, N180R, P183T, P183G, Q184E, Q184K, R185G,Y196W, Y196F, N200T, 5202R, Q203T, R205K, R210L, R210G, R210M, N213V,N213D, T228S, N229D, E234F, E234Y, A235K, A235R, S241C, Q243K, Q243E,R244K, R244V, A250G, K254Y, G257W, G257E, G257A, G257G, W260F, W260Y,W260L, W260T, Y262F, S266A, D268N, A270D, N272M, N272T, N273E, N273D,A276E, A276W, A276D, N279D, N279E, T280L, N283W, N283H, Y286W, Y286F,L288I, E290A, L294P, L294K, L294I, L294R, L294V, L294H, S295K, S295V,S295P, S295L, S295R, S295A, S295N, S295M, S295I, T296S, and F298Y.

Accordingly, the at least two substitutions may be any combination ofthose listed herein. Such at least two substitutions may be selectedfrom the group consisting of: A1G+N2E, A1G+S3P, A1G+G4D, A1G+F5H,A1G+Y6H, A1G+Y6M, A1G+Y6F, A1G+Y6W, A1G+Y6H, A1G+S8T, A1G+S8P, A1G+S8R,A1G+T11K, A1G+T11R, A1G+Y13F, A1G+D14S, A1G+D14K, A1G+N18V, A1G+N18R,A1G+A30T, A1G+Y32F, A1G+Y32W, A1G+K33Q, A1G+D34G, A1G+Q35L, A1G+T37P,A1G+E41V, A1G+E41N, A1G+N45G, A1G+G47S, A1G+G47A, A1G+D57N, A1G+G59Q,A1G+Q60R, A1G+K63R, A1G+K63Q, A1G+D65E, A1G+R70K, A1G+N71S, A1G+S74K,A1G+E77T, A1G+E77N, A1G+D78G, A1G+H80K, A1G+V82R, A1G+V82I, A1G+V82S,A1G+A83P, A1G+A83S, A1G+Y93Q, A1G+Y93A, A1G+S95D, A1G+A97R, A1G+S98P,A1G+S98D, A1G+N100Y, A1G+D104A, A1G+D104G, A1G+E108S, A1G+S111A,A1G+S111K, A1G+S111R, A1G+I114Q, A1G+I114M, A1G+I114W, A1G+K116R,A1G+D118K, A1G+T119R, A1G+S131T, A1G+E133R, A1G+E133Q, A1G+D135P,A1G+A136P, A1G+D139A, A1G+D139R, A1G+K142M, A1G+K142V, A1G+K142S,A1G+K142R, A1G+Q143R, A1G+N150T, A1G+N150R, A1G+N150S, A1G+Q169A,A1G+Q169R, A1G+Q169K, A1G+H172R, A1G+Y174R, A1G+Y174L, A1G+Y174W,A1G+Y174F, A1G+R176Q, A1G+E177S, A1G+E177Y, A1G+N180R, A1G+P183T,A1G+P183G, A1G+Q184E, A1G+Q184K, A1G+R185G, A1G+Y196W, A1G+Y196F,A1G+N200T, A1G+S202R, A1G+Q203T, A1G+R205K, A1G+R210L, A1G+R210G,A1G+R210M, A1G+N213V, A1G+N213D, A1G+T228S, A1G+N229D, A1G+E234F,A1G+E234Y, A1G+A235K, A1G+A235R, A1G+S241C, A1G+Q243K, A1G+Q243E,A1G+R244K, A1G+R244V, A1G+A250G, A1G+K254Y, A1G+G257W, A1G+G257E,A1G+G257A, A1G+W260F, A1G+Y262F, A1G+S266A, A1G+D268N, A1G+A270D,A1G+N272M, A1G+N272T, A1G+N273E, A1G+N273D, A1G+A276E, A1G+A276W,A1G+A276D, A1G+N279D, A1G+N279E, A1G+T280L, A1G+N283W, A1G+N283H,A1G+Y286W, A1G+Y286F, A1G+L288I, A1G+E290A, A1G+L294P, A1G+L294K,A1G+L294I, A1G+L294R, A1G+L294V, A1G+L294H, A1G+S295K, A1G+S295V,A1G+S295P, A1G+S295L, A1G+S295R, A1G+S295A, A1G+S295N, A1G+S295M,A1G+S295I, A1G+T296S, A1G+F298Y, A1V+N2E, A1V+S3P, A1V+G4D, A1V+F5H,A1V+Y6H, A1V+Y6M, A1V+Y6F, A1V+Y6W, A1V+Y6H, A1V+S8T, A1V+S8P, A1V+S8R,A1V+T11K, A1V+T11R, A1V+Y13F, A1V+D14S, A1V+D14K, A1V+N18V, A1V+N18R,A1V+A30T, A1V+Y32F, A1V+Y32W, A1V+K33Q, A1V+D34G, A1V+Q35L, A1V+T37P,A1V+E41V, A1V+E41N, A1V+N45G, A1V+G47S, A1V+G47A, A1V+D57N, A1V+G59Q,A1V+Q60R, A1V+K63R, A1V+K63Q, A1V+D65E, A1V+R70K, A1V+N71S, A1V+S74K,A1V+E77T, A1V+E77N, A1V+D78G, A1V+H80K, A1V+V82R, A1V+V82I, A1V+V82S,A1V+A83P, A1V+A83S, A1V+Y93Q, A1V+Y93A, A1V+S95D, A1V+A97R, A1V+S98P,A1V+S98D, A1V+N100Y, A1V+D104A, A1V+D104G, A1V+E108S, A1V+S111A,A1V+S111K, A1V+S111R, A1V+I114Q, A1V+I114M, A1V+I114W, A1V+K116R,A1V+D118K, A1V+T119R, A1V+S131T, A1V+E133R, A1V+E133Q, A1V+D135P,A1V+A136P, A1V+D139A, A1V+D139R, A1V+K142M, A1V+K142V, A1V+K142S,A1V+K142R, A1V+Q143R, A1V+N150T, A1V+N150R, A1V+N150S, A1V+Q169A,A1V+Q169R, A1V+Q169K, A1V+H172R, A1V+Y174R, A1V+Y174L, A1V+Y174W,A1V+Y174F, A1V+R176Q, A1V+E177S, A1V+E177Y, A1V+N180R, A1V+P 183T,A1V+P183G, A1V+Q184E, A1V+Q184K, A1V+R185G, A1V+Y196W, A1V+Y196F,A1V+N200T, A1V+S202R, A1V+Q203T, A1V+R205K, A1V+R210L, A1V+R210G,A1V+R210M, A1V+N213V, A1V+N213D, A1V+T228S, A1V+N229D, A1V+E234F,A1V+E234Y, A1V+A235K, A1V+A235R, A1V+S241C, A1V+Q243K, A1V+Q243E,A1V+R244K, A1V+R244V, A1V+A250G, A1V+K254Y, A1V+G257W, A1V+G257 E,A1V+G257A, A1V+W260F, A1V+W260Y, A1V+W260L, A1V+W260T, A1V+Y262F,A1V+S266A, A1V+D268N, A1V+A270D, A1V+N272M, A1V+N272T, A1V+N273E,A1V+N273D, A1V+A276E, A1V+A276W, A1V+A276D, A1V+N279D, A1V+N279E,A1V+T280L, A1V+N283W, A1V+N283H, A1V+Y286W, A1V+Y286F, A1V+L288I,A1V+E290A, A1V+L294P, A1V+L294K, A1V+L294I, A1V+L294R, A1V+L294V,A1V+L294H, A1V+S295K, A1V+S295V, A1V+S295P, A1V+S295L, A1V+S295R,A1V+S295A, A1V+S295N, A1V+S295M, A1V+S295I, A1V+T296S, A1V+F298Y,N2E+S3P, N2E+G4D, N2E+F5H, N2E+Y6H, N2E+Y6M, N2E+Y6F, N2E+Y6W, N2E+Y6H,N2E+S8T, N2E+S8P, N2E+S8R, N2E+T11K, N2E+T11R, N2E+Y13F, N2E+D14S,N2E+D14K, N2E+N18V, N2E+N 1 8R, N2E+A30T, N2E+Y32F, N2E+Y32W, N2E+K33Q,N2E+D34G, N2E+Q35L, N2E+T37P, N2E+E41V, N2E+E41N, N2E+N45G, N2E+G47S,N2E+G47A, N2E+D57N, N2E+G59Q, N2E+Q60R, N2E+K63R, N2E+K63Q, N2E+D65E,N2E+R70K, N2E+N71S, N2E+S74K, N2E+E77T, N2E+E77N, N2E+D78G, N2E+H80K,N2E+V82R, N2E+V82I, N2E+V82S, N2E+A83P, N2E+A83S, N2E+Y93Q, N2E+Y93A,N2E+S95D, N2E+A97R, N2E+S98P, N2E+S98D, N2E+N100Y, N2E+D104A, N2E+D104G,N2E+E108S, N2E+S111A, N2E+S111K, N2E+S111R, N2E+I114Q, N2E+I114M,N2E+I114W, N2E+K116R, N2E+D118K, N2E+T119R, N2E+S131T, N2E+E133R,N2E+E133Q, N2E+D135P, N2E+A136P, N2E+D139A, N2E+D139R, N2E+K142M,N2E+K142V, N2E+K142S, N2E+K142R, N2E+Q143R, N2E+N150T, N2E+N150R,N2E+N150S, N2E+Q169A, N2E+Q169R, N2E+Q169K, N2E+H172R, N2E+Y174R,N2E+Y174L, N2E+Y174W, N2E+Y174F, N2E+R176Q, N2E+E177S, N2E+E177Y,N2E+N180R, N2E+P183T, N2E+P183G, N2E+Q184E, N2E+Q184K, N2E+R185G,N2E+Y196W, N2E+Y196F, N2E+N200T, N2E+S202R, N2E+Q203T, N2E+R205K,N2E+R210L, N2E+R210G, N2E+R210M, N2E+N213V, N2E+N213D, N2E+T228S,N2E+N229D, N2E+E234F, N2E+E234Y, N2E+A235K, N2E+A235R, N2E+S241C,N2E+Q243K, N2E+Q243E, N2E+R244K, N2E+R244V, N2E+A250G, N2E+K254Y,N2E+G257W, N2E+G257E, N2E+G257A, N2E+W260F, N2E+W260Y, N2E+W260L,N2E+W260T, N2E+Y262F, N2E+S266A, N2E+D268N, N2E+A270D, N2E+N272M,N2E+N272T, N2E+N273E, N2E+N273D, N2E+A276E, N2E+A276W, N2E+A276D,N2E+N279D, N2E+N279E, N2E+T280L, N2E+N283W, N2E+N283H, N2E+Y286W,N2E+Y286F, N2E+L288I, N2E+E290A, N2E+L294P, N2E+L294K, N2E+L294I,N2E+L294R, N2E+L294V, N2E+L294H, N2E+S295K, N2E+S295V, N2E+S295P,N2E+S295L, N2E+S295R, N2E+S295A, N2E+S295N, N2E+S295M, N2E+S295I,N2E+T296S, N2E+F298Y, S3P+G4D, S3P+F5H, S3P+Y6H, S3P+Y6M, S3P+Y6F,S3P+Y6W, S3P+Y6H, S3P+S8T, S3P+S8P, S3P+S8R, S3P+T11K, S3P+T11R,S3P+Y13F, S3P+D14S, S3P+D14K, S3P+N18V, S3P+N18R, S3P+A30T, S3P+Y32F,S3P+Y32W, S3P+K33Q, S3P+D34G, S3P+Q35L, S3P+T37P, S3P+E41V, S3P+E41N,S3P+N45G, S3P+G47S, S3P+G47A, S3P+D57N, S3P+G59Q, S3P+Q60R, S3P+K63R,S3P+K63Q, S3P+D65E, S3P+R70K, S3P+N71S, S3P+S74K, S3P+E77T, S3P+E77N,S3P+D78G, S3P+H80K, S3P+V82R, S3P+V82I, S3P+V82S, S3P+A83P, S3P+A83S,S3P+Y93Q, S3P+Y93A, S3P+S95D, S3P+A97R, S3P+S98P, S3P+S98D, S3P+N100Y,S3P+D104A, S3P+D104G, S3P+E108S, S3P+S111A, S3P+S111 K, S3P+S111R,S3P+I114Q, S3P+I114M, S3P+I114W, S3P+K116R, S3P+D118K, S3P+T119R,S3P+S131T, S3P+E133R, S3P+E133Q, S3P+D135P, S3P+A136P, S3P+D139A,S3P+D139R, S3P+K142M, S3P+K142V, S3P+K142S, S3P+K142R, S3P+Q143R,S3P+N150T, S3P+N150R, S3P+N150S, S3P+Q169A, S3P+Q169R, S3P+Q169K,S3P+H172R, S3P+Y174R, S3P+Y174L, S3P+Y174W, S3P+Y174F, S3P+R176Q,S3P+E177S, S3P+E177Y, S3P+N180R, S3P+P183T, S3P+P183G, S3P+Q184E,S3P+Q184K, S3P+R185G, S3P+Y196W, S3P+Y196F, S3P+N200T, S3P+S202R,S3P+Q203T, S3P+R205K, S3P+R210L, S3P+R210G, S3P+R210M, S3P+N213V,S3P+N213D, S3P+T228S, S3P+N229D, S3P+E234F, S3P+E234Y, S3P+A235K,S3P+A235R, S3P+S241C, S3P+Q243K, S3P+Q243E, S3P+R244K, S3P+R244V,S3P+A250G, S3P+K254Y, S3P+G257W, S3P+G257E, S3P+G257A, S3P+W260F,S3P+W260Y, S3P+W260L, S3P+W260T, S3P+Y262F, S3P+S266A, S3P+D268N,S3P+A270D, S3P+N272M, S3P+N272T, S3P+N273E, S3P+N273D, S3P+A276E,S3P+A276W, S3P+A276D, S3P+N279D, S3P+N279E, S3P+T280L, S3P+N283W,S3P+N283H, S3P+Y286W, S3P+Y286F, S3P+L288I, S3P+E290A, S3P+L294P,S3P+L294K, S3P+L294I, S3P+L294R, S3P+L294V, S3P+L294H, S3P+S295K,S3P+S295V, S3P+S295P, S3P+S295L, S3P+S295R, S3P+S295A, S3P+S295N,S3P+S295M, S3P+S295I, S3P+T296S, S3P+F298Y, G4D+F5H, G4D+Y6H, G4D+Y6M,G4D+Y6F, G4D+Y6W, G4D+Y6H, G4D+S8T, G4D+S8P, G4D+S8R, G4D+T11K,G4D+T11R, G4D+Y13F, G4D+D14S, G4D+D14K, G4D+N18V, G4D+N18R, G4D+A30T,G4D+Y32F, G4D+Y32W, G4D+K33Q, G4D+D34G, G4D+Q35L, G4D+T37P, G4D+E41V,G4D+E41N, G4D+N45G, G4D+G47S, G4D+G47A, G4D+D57N, G4D+G59Q, G4D+Q60R,G4D+K63R, G4D+K63Q, G4D+D65E, G4D+R70K, G4D+N71S, G4D+S74K, G4D+E77T,G4D+E77N, G4D+D78G, G4D+H80K, G4D+V82R, G4D+V82I, G4D+V82S, G4D+A83P,G4D+A83S, G4D+Y93Q, G4D+Y93A, G4D+S95D, G4D+A97R, G4D+S98P, G4D+S98D,G4D+N100Y, G4D+D104A, G4D+D104G, G4D+E108S, G4D+S111A, G4D+S111K,G4D+S111R, G4D+I114Q, G4D+I114M, G4D+I114W, G4D+K116R, G4D+D118K,G4D+T119R, G4D+S131T, G4D+E133R, G4D+E133Q, G4D+D135P, G4D+A136P,G4D+D139A, G4D+D139R, G4D+K142M, G4D+K142V, G4D+K142S, G4D+K142R,G4D+Q143R, G4D+N150T, G4D+N150R, G4D+N150S, G4D+Q169A, G4D+Q169R,G4D+Q169K, G4D+H172R, G4D+Y174R, G4D+Y174L, G4D+Y174W, G4D+Y174F,G4D+R176Q, G4D+E177S, G4D+E177Y, G4D+N180R, G4D+P183T, G4D+P183G,G4D+Q184E, G4D+Q184K, G4D+R185G, G4D+Y196W, G4D+Y196F, G4D+N200T,G4D+S202R, G4D+Q203T, G4D+R205K, G4D+R210L, G4D+R210G, G4D+R210M,G4D+N213V, G4D+N213D, G4D+T228S, G4D+N229D, G4D+E234F, G4D+E234Y,G4D+A235K, G4D+A235R, G4D+S241C, G4D+Q243K, G4D+Q243E, G4D+R244K,G4D+R244V, G4D+A250G, G4D+K254Y, G4D+G257W, G4D+G257E, G4D+G257A,G4D+W260F, G4D+W260Y, G4D+W260L, G4D+W260T, G4D+Y262F, G4D+S266A,G4D+D268N, G4D+A270D, G4D+N272M, G4D+N272T, G4D+N273E, G4D+N273D,G4D+A276E, G4D+A276W, G4D+A276D, G4D+N279D, G4D+N279E, G4D+T280L,G4D+N283W, G4D+N283H, G4D+Y286W, G4D+Y286F, G4D+L288I, G4D+E290A,G4D+L294P, G4D+L294K, G4D+L294I, G4D+L294R, G4D+L294V, G4D+L294H,G4D+S295K, G4D+S295V, G4D+S295P, G4D+S295L, G4D+S295R, G4D+S295A,G4D+S295N, G4D+S295M, G4D+S295I, G4D+T296S, G4D+F298Y, F5H+Y6H, F5H+Y6M,F5H+Y6F, F5H+Y6W, F5H+Y6H, F5H+S8T, F5H+S8P, F5H+S8R, F5H+T11K,F5H+T11R, F5H+Y13F, F5H+D14S, F5H+D14K, F5H+N18V, F5H+N18R, F5H+A30T,F5H+Y32F, F5H+Y32W, F5H+K33Q, F5H+D34G, F5H+Q35L, F5H+T37P, F5H+E41V,F5H+E41N, F5H+N45G, F5H+G47S, F5H+G47A, F5H+D57N, F5H+G59Q, F5H+Q60R,F5H+K63R, F5H+K63Q, F5H+D65E, F5H+R70K, F5H+N71S, F5H+S74K, F5H+E77T,F5H+E77N, F5H+D78G, F5H+H80K, F5H+V82R, F5H+V82I, F5H+V82S, F5H+A83P,F5H+A83S, F5H+Y93Q, F5H+Y93A, F5H+S95D, F5H+A97R, F5H+S98P, F5H+S98D,F5H+N100Y, F5H+D104A, F5H+D104G, F5H+E108S, F5H+S111A, F5H+S111K,F5H+S111R, F5H+I114Q, F5H+I114M, F5H+I114W, F5H+K116R, F5H+D118K,F5H+T119R, F5H+S131T, F5H+E133R, F5H+E133Q, F5H+D135P, F5H+A136P,F5H+D139A, F5H+D139R, F5H+K142M, F5H+K142V, F5H+K142S, F5H+K142R,F5H+Q143R, F5H+N150T, F5H+N150R, F5H+N150S, F5H+Q169A, F5H+Q169R,F5H+Q169K, F5H+H172R, F5H+Y174R, F5H+Y174L, F5H+Y174W, F5H+Y174F,F5H+R176Q, F5H+E177S, F5H+E177Y, F5H+N180R, F5H+P183T, F5H+P183G,F5H+Q184E, F5H+Q184K, F5H+R185G, F5H+Y196W, F5H+Y196F, F5H+N200T,F5H+S202R, F5H+Q203T, F5H+R205K, F5H+R210L, F5H+R210G, F5H+R210M,F5H+N213V, F5H+N213D, F5H+T228S, F5H+N229D, F5H+E234F, F5H+E234Y,F5H+A235K, F5H+A235R, F5H+S241C, F5H+Q243K, F5H+Q243E, F5H+R244K,F5H+R244V, F5H+A250G, F5H+K254Y, F5H+G257W, F5H+G257E, F5H+G257A,F5H+W260F, F5H+W260Y, F5H+W260L, F5H+W260T, F5H+Y262F, F5H+S266A,F5H+D268N, F5H+A270D, F5H+N272M, F5H+N272T, F5H+N273E, F5H+N273D,F5H+A276E, F5H+A276W, F5H+A276D, F5H+N279D, F5H+N279E, F5H+T280L,F5H+N283W, F5H+N283H, F5H+Y286W, F5H+Y286F, F5H+L288I, F5H+E290A,F5H+L294P, F5H+L294K, F5H+L294I, F5H+L294R, F5H+L294V, F5H+L294H,F5H+S295K, F5H+S295V, F5H+S295P, F5H+S295L, F5H+S295R, F5H+S295A,F5H+S295N, F5H+S295M, F5H+S295I, F5H+T296S, F5H+F298Y, Y6H+S8T, Y6H+S8P,Y6H+S8R, Y6H+T11K, Y6H+T11R, Y6H+Y13F, Y6H+D14S, Y6H+D14K, Y6H+N18V,Y6H+N18R, Y6H+A30T, Y6H+Y32F, Y6H+Y32W, Y6H+K33Q, Y6H+D34G, Y6H+Q35L,Y6H+T37P, Y6H+E41V, Y6H+E41N, Y6H+N45G, Y6H+G47S, Y6H+G47A, Y6H+D57N,Y6H+G59Q, Y6H+Q60R, Y6H+K63R, Y6H+K63Q, Y6H+D65E, Y6H+R70K, Y6H+N71S,Y6H+S74K, Y6H+E77T, Y6H+E77N, Y6H+D78G, Y6H+H80K, Y6H+V82R, Y6H+V82I,Y6H+V82S, Y6H+A83P, Y6H+A83S, Y6H+Y93Q, Y6H+Y93A, Y6H+S95D, Y6H+A97R,Y6H+S98P, Y6H+S98D, Y6H+N100Y, Y6H+D104A, Y6H+D104G, Y6H+E108S,Y6H+S111A, Y6H+S111K, Y6H+S111R, Y6H+I114Q, Y6H+I114M, Y6H+I114W,Y6H+K116R, Y6H+D118K, Y6H+T119R, Y6H+S131T, Y6H+E133R, Y6H+E133Q,Y6H+D135P, Y6H+A136P, Y6H+D139A, Y6H+D139R, Y6H+K142M, Y6H+K142V,Y6H+K142S, Y6H+K142R, Y6H+Q143R, Y6H+N150T, Y6H+N150R, Y6H+N150S,Y6H+Q169A, Y6H+Q169R, Y6H+Q169K, Y6H+H172R, Y6H+Y174R, Y6H+Y174L,Y6H+Y174W, Y6H+Y174F, Y6H+R176Q, Y6H+E177S, Y6H+E177Y, Y6H+N180R,Y6H+P183T, Y6H+P183G, Y6H+Q184E, Y6H+Q184K, Y6H+R185G, Y6H+Y196W,Y6H+Y196F, Y6H+N200T, Y6H+S202R, Y6H+Q203T, Y6H+R205K, Y6H+R210L,Y6H+R210G, Y6H+R210M, Y6H+N213V, Y6H+N213D, Y6H+T228S, Y6H+N229D,Y6H+E234F, Y6H+E234Y, Y6H+A235K, Y6H+A235R, Y6H+S241C, Y6H+Q243K,Y6H+Q243E, Y6H+R244K, Y6H+R244V, Y6H+A250G, Y6H+K254Y, Y6H+G257W,Y6H+G257E, Y6H+G257A, Y6H+W260F, Y6H+W260Y, Y6H+W260L, Y6H+W260T,Y6H+Y262F, Y6H+S266A, Y6H+D268N, Y6H+A270D, Y6H+N272M, Y6H+N272T,Y6H+N273E, Y6H+N273D, Y6H+A276E, Y6H+A276W, Y6H+A276D, Y6H+N279D,Y6H+N279E, Y6H+T280L, Y6H+N283W, Y6H+N283H, Y6H+Y286W, Y6H+Y286F,Y6H+L288I, Y6H+E290A, Y6H+L294P, Y6H+L294K, Y6H+L294I, Y6H+L294R,Y6H+L294V, Y6H+L294H, Y6H+S295K, Y6H+S295V, Y6H+S295P, Y6H+S295L,Y6H+S295R, Y6H+S295A, Y6H+S295N, Y6H+S295M, Y6H+S295I, Y6H+T296S,Y6H+F298Y, Y6M+S8T, Y6M+S8P, Y6M+S8R, Y6M+T11K, Y6M+T11R, Y6M+Y13F,Y6M+D14S, Y6M+D14K, Y6M+N18V, Y6M+N18R, Y6M+A30T, Y6M+Y32F, Y6M+Y32W,Y6M+K33Q, Y6M+D34G, Y6M+Q35L, Y6M+T37P, Y6M+E41V, Y6M+E41N, Y6M+N45G,Y6M+G47S, Y6M+G47A, Y6M+D57N, Y6M+G59Q, Y6M+Q60R, Y6M+K63R, Y6M+K63Q,Y6M+D65E, Y6M+R70K, Y6M+N71S, Y6M+S74K, Y6M+E77T, Y6M+E77N, Y6M+D78G,Y6M+H80K, Y6M+V82R, Y6M+V82I, Y6M+V82S, Y6M+A83P, Y6M+A83S, Y6M+Y93Q,Y6M+Y93A, Y6M+S95D, Y6M+A97R, Y6M+S98P, Y6M+S98D, Y6M+N100Y, Y6M+D104A,Y6M+D104G, Y6M+E108S, Y6M+S111A, Y6M+S111K, Y6M+S111R, Y6M+I114Q,Y6M+I114M, Y6M+I114W, Y6M+K116R, Y6M+D118K, Y6M+T119R, Y6M+S131T,Y6M+E133R, Y6M+E133Q, Y6M+D135P, Y6M+A136P, Y6M+D139A, Y6M+D139R,Y6M+K142M, Y6M+K142V, Y6M+K142S, Y6M+K142R, Y6M+Q143R, Y6M+N150T,Y6M+N150R, Y6M+N150S, Y6M+Q169A, Y6M+Q169R, Y6M+Q169K, Y6M+H172R,Y6M+Y174R, Y6M+Y174L, Y6M+Y174W, Y6M+Y174F, Y6M+R176Q, Y6M+E177S,Y6M+E177Y, Y6M+N180R, Y6M+P183T, Y6M+P183G, Y6M+Q184E, Y6M+Q184K,Y6M+R185G, Y6M+Y196W, Y6M+Y196F, Y6M+N200T, Y6M+S202R, Y6M+Q203T,Y6M+R205K, Y6M+R210L, Y6M+R210G, Y6M+R210M, Y6M+N213V, Y6M+N213D,Y6M+T228S, Y6M+N229D, Y6M+E234F, Y6M+E234Y, Y6M+A235K, Y6M+A235R,Y6M+S241C, Y6M+Q243K, Y6M+Q243E, Y6M+R244K, Y6M+R244V, Y6M+A250G,Y6M+K254Y, Y6M+G257W, Y6M+G257E, Y6M+G257A, Y6M+W260F, Y6M+W260Y,Y6M+W260L, Y6M+W260T, Y6M+Y262F, Y6M+S266A, Y6M+D268N, Y6M+A270D,Y6M+N272M, Y6M+N272T, Y6M+N273E, Y6M+N273D, Y6M+A276E, Y6M+A276W,Y6M+A276D, Y6M+N279D, Y6M+N279E, Y6M+T280L, Y6M+N283W, Y6M+N283H,Y6M+Y286W, Y6M+Y286F, Y6M+L288I, Y6M+E290A, Y6M+L294P, Y6M+L294K,Y6M+L294I, Y6M+L294R, Y6M+L294V, Y6M+L294H, Y6M+S295K, Y6M+S295V,Y6M+S295P, Y6M+S295L, Y6M+S295R, Y6M+S295A, Y6M+S295N, Y6M+S295M,Y6M+S295I, Y6M+T296S, Y6M+F298Y, Y6F+S8T, Y6F+S8P, Y6F+S8R, Y6F+T11K,Y6F+T11R, Y6F+Y13F, Y6F+D14S, Y6F+D14K, Y6F+N18V, Y6F+N18R, Y6F+A30T,Y6F+Y32F, Y6F+Y32W, Y6F+K33Q, Y6F+D34G, Y6F+Q35L, Y6F+T37P, Y6F+E41V,Y6F+E41N, Y6F+N45G, Y6F+G47S, Y6F+G47A, Y6F+D57N, Y6F+G59Q, Y6F+Q60R,Y6F+K63R, Y6F+K63Q, Y6F+D65E, Y6F+R70K, Y6F+N71S, Y6F+S74K, Y6F+E77T,Y6F+E77N, Y6F+D78G, Y6F+H80K, Y6F+V82R, Y6F+V82I, Y6F+V82S, Y6F+A83P,Y6F+A83S, Y6F+Y93Q, Y6F+Y93A, Y6F+S95D, Y6F+A97R, Y6F+S98P, Y6F+S98D,Y6F+N100Y, Y6F+D104A, Y6F+D104G, Y6F+E108S, Y6F+S111A, Y6F+S111K,Y6F+S111R, Y6F+I114Q, Y6F+I114M, Y6F+I114W, Y6F+K116R, Y6F+D118K,Y6F+T119R, Y6F+S131T, Y6F+E133R, Y6F+E133Q, Y6F+D135P, Y6F+A136P,Y6F+D139A, Y6F+D139R, Y6F+K142M, Y6F+K142V, Y6F+K142S, Y6F+K142R,Y6F+Q143R, Y6F+N150T, Y6F+N150R, Y6F+N150S, Y6F+Q169A, Y6F+Q169R,Y6F+Q169K, Y6F+H172R, Y6F+Y174R, Y6F+Y174L, Y6F+Y174W, Y6F+Y174F,Y6F+R176Q, Y6F+E177S, Y6F+E177Y, Y6F+N180R, Y6F+P183T, Y6F+P183G,Y6F+Q184E, Y6F+Q184K, Y6F+R185G, Y6F+Y196W, Y6F+Y196F, Y6F+N200T,Y6F+S202R, Y6F+Q203T, Y6F+R205K, Y6F+R210L, Y6F+R210G, Y6F+R210M,Y6F+N213V, Y6F+N213D, Y6F+T228S, Y6F+N229D, Y6F+E234F, Y6F+E234Y,Y6F+A235K, Y6F+A235R, Y6F+S241C, Y6F+Q243K, Y6F+Q243E, Y6F+R244K,Y6F+R244V, Y6F+A250G, Y6F+K254Y, Y6F+G257W, Y6F+G257E, Y6F+G257A,Y6F+W260F, Y6F+W260Y, Y6F+W260L, Y6F+W260T, Y6F+Y262F, Y6F+S266A,Y6F+D268N, Y6F+A270D, Y6F+N272M, Y6F+N272T, Y6F+N273E, Y6F+N273D,Y6F+A276E, Y6F+A276W, Y6F+A276D, Y6F+N279D, Y6F+N279E, Y6F+T280L,Y6F+N283W, Y6F+N283H, Y6F+Y286W, Y6F+Y286F, Y6F+L288I, Y6F+E290A,Y6F+L294P, Y6F+L294K, Y6F+L294I, Y6F+L294R, Y6F+L294V, Y6F+L294H,Y6F+S295K, Y6F+S295V, Y6F+S295P, Y6F+S295L, Y6F+S295R, Y6F+S295A,Y6F+S295N, Y6F+S295M, Y6F+S295I, Y6F+T296S, Y6F+F298Y, Y6W+S8T, Y6W+S8P,Y6W+S8R, Y6W+T11K, Y6W+T11R, Y6W+Y13F, Y6W+D14S, Y6W+D14K, Y6W+N18V,Y6W+N18R, Y6W+A30T, Y6W+Y32F, Y6W+Y32W, Y6W+K33Q, Y6W+D34G, Y6W+Q35L,Y6W+T37P, Y6W+E41V, Y6W+E41N, Y6W+N45G, Y6W+G47S, Y6W+G47A, Y6W+D57N,Y6W+G59Q, Y6W+Q60R, Y6W+K63R, Y6W+K63Q, Y6W+D65E, Y6W+R70K, Y6W+N71S,Y6W+S74K, Y6W+E77T, Y6W+E77N, Y6W+D78G, Y6W+H80K, Y6W+V82R, Y6W+V82I,Y6W+V82S, Y6W+A83P, Y6W+A83S, Y6W+Y93Q, Y6W+Y93A, Y6W+S95D, Y6W+A97R,Y6W+S98P, Y6W+S98D, Y6W+N100Y, Y6W+D104A, Y6W+D104G, Y6W+E108S,Y6W+S111A, Y6W+S111K, Y6W+S111R, Y6W+I114Q, Y6W+I114M, Y6W+I114W,Y6W+K116R, Y6W+D118K, Y6W+T119R, Y6W+S131T, Y6W+E133R, Y6W+E133Q,Y6W+D135P, Y6W+A136P, Y6W+D139A, Y6W+D139R, Y6W+K142M, Y6W+K142V,Y6W+K142S, Y6W+K142R, Y6W+Q143R, Y6W+N150T, Y6W+N150R, Y6W+N150S,Y6W+Q169A, Y6W+Q169R, Y6W+Q169K, Y6W+H172R, Y6W+Y174R, Y6W+Y174L,Y6W+Y174W, Y6W+Y174F, Y6W+R176Q, Y6W+E177S, Y6W+E177Y, Y6W+N180R,Y6W+P183T, Y6W+P183G, Y6W+Q184E, Y6W+Q184K, Y6W+R185G, Y6W+Y196W,Y6W+Y196F, Y6W+N200T, Y6W+S202R, Y6W+Q203T, Y6W+R205K, Y6W+R210L,Y6W+R210G, Y6W+R210M, Y6W+N213V, Y6W+N213D, Y6W+T228S, Y6W+N229D,Y6W+E234F, Y6W+E234Y, Y6W+A235K, Y6W+A235R, Y6W+S241C, Y6W+Q243K,Y6W+Q243E, Y6W+R244K, Y6W+R244V, Y6W+A250G, Y6W+K254Y, Y6W+G257W,Y6W+G257E, Y6W+G257A, Y6W+W260F, Y6W+W260Y, Y6W+W260L, Y6W+W260T,Y6W+Y262F, Y6W+S266A, Y6W+D268N, Y6W+A270D, Y6W+N272M, Y6W+N272T,Y6W+N273E, Y6W+N273D, Y6W+A276E, Y6W+A276W, Y6W+A276D, Y6W+N279D,Y6W+N279E, Y6W+T280L, Y6W+N283W, Y6W+N283H, Y6W+Y286W, Y6W+Y286F,Y6W+L288I, Y6W+E290A, Y6W+L294P, Y6W+L294K, Y6W+L294I, Y6W+L294R,Y6W+L294V, Y6W+L294H, Y6W+S295K, Y6W+S295V, Y6W+S295P, Y6W+S295L,Y6W+S295R, Y6W+S295A, Y6W+S295N, Y6W+S295M, Y6W+S295I, Y6W+T296S,Y6W+F298Y, Y6H+S8T, Y6H+S8P, Y6H+S8R, Y6H+T11K, Y6H+T11R, Y6H+Y13F,Y6H+D14S, Y6H+D14K, Y6H+N18V, Y6H+N18R, Y6H+A30T, Y6H+Y32F, Y6H+Y32W,Y6H+K33Q, Y6H+D34G, Y6H+Q35L, Y6H+T37P, Y6H+E41V, Y6H+E41N, Y6H+N45G,Y6H+G47S, Y6H+G47A, Y6H+D57N, Y6H+G59Q, Y6H+Q60R, Y6H+K63R, Y6H+K63Q,Y6H+D65E, Y6H+R70K, Y6H+N71S, Y6H+S74K, Y6H+E77T, Y6H+E77N, Y6H+D78G,Y6H+H80K, Y6H+V82R, Y6H+V82I, Y6H+V82S, Y6H+A83P, Y6H+A83S, Y6H+Y93Q,Y6H+Y93A, Y6H+S95D, Y6H+A97R, Y6H+S98P, Y6H+S98D, Y6H+N100Y, Y6H+D104A,Y6H+D104G, Y6H+E108S, Y6H+S111A, Y6H+S111K, Y6H+S111R, Y6H+I114Q,Y6H+I114M, Y6H+I114W, Y6H+K116R, Y6H+D118K, Y6H+T119R, Y6H+S131T,Y6H+E133R, Y6H+E133Q, Y6H+D135P, Y6H+A136P, Y6H+D139A, Y6H+D139R,Y6H+K142M, Y6H+K142V, Y6H+K142S, Y6H+K142R, Y6H+Q143R, Y6H+N150T,Y6H+N150R, Y6H+N150S, Y6H+Q169A, Y6H+Q169R, Y6H+Q169K, Y6H+H172R,Y6H+Y174R, Y6H+Y174L, Y6H+Y174W, Y6H+Y174F, Y6H+R176Q, Y6H+E177S,Y6H+E177Y, Y6H+N180R, Y6H+P183T, Y6H+P183G, Y6H+Q184E, Y6H+Q184K,Y6H+R185G, Y6H+Y196W, Y6H+Y196F, Y6H+N200T, Y6H+S202R, Y6H+Q203T,Y6H+R205K, Y6H+R210L, Y6H+R210G, Y6H+R210M, Y6H+N213V, Y6H+N213D,Y6H+T228S, Y6H+N229D, Y6H+E234F, Y6H+E234Y, Y6H+A235K, Y6H+A235R,Y6H+S241C, Y6H+Q243K, Y6H+Q243E, Y6H+R244K, Y6H+R244V, Y6H+A250G,Y6H+K254Y, Y6H+G257W, Y6H+G257E, Y6H+G257A, Y6H+W260F, Y6H+W260Y,Y6H+W260L, Y6H+W260T, Y6H+Y262F, Y6H+S266A, Y6H+D268N, Y6H+A270D,Y6H+N272M, Y6H+N272T, Y6H+N273E, Y6H+N273D, Y6H+A276E, Y6H+A276W,Y6H+A276D, Y6H+N279D, Y6H+N279E, Y6H+T280L, Y6H+N283W, Y6H+N283H,Y6H+Y286W, Y6H+Y286F, Y6H+L288I, Y6H+E290A, Y6H+L294P, Y6H+L294K,Y6H+L294I, Y6H+L294R, Y6H+L294V, Y6H+L294H, Y6H+S295K, Y6H+S295V,Y6H+S295P, Y6H+S295L, Y6H+S295R, Y6H+S295A, Y6H+S295N, Y6H+S295M,Y6H+S295I, Y6H+T296S, Y6H+F298Y, S8T+T11K, S8T+T11R, S8T+Y13F, S8T+D14S,S8T+D14K, S8T+N18V, S8T+N18R, S8T+A30T, S8T+Y32F, S8T+Y32W, S8T+K33Q,S8T+D34G, S8T+Q35L, S8T+T37P, S8T+E41V, S8T+E41 N, S8T+N45G, S8T+G47S,S8T+G47A, S8T+D57N, S8T+G59Q, S8T+Q60R, S8T+K63R, S8T+K63Q, S8T+D65E,S8T+R70K, S8T+N71S, S8T+S74K, S8T+E77T, S8T+E77N, S8T+D78G, S8T+H80K,S8T+V82R, S8T+V82I, S8T+V82S, S8T+A83P, S8T+A83S, S8T+Y93Q, S8T+Y93A,S8T+S95D, S8T+A97R, S8T+S98P, S8T+S98D, S8T+N100Y, S8T+D104A, S8T+D104G,S8T+E108S, S8T+S111A, S8T+S111K, S8T+S111R, S8T+I114Q, S8T+I114M,S8T+I114W, S8T+K116R, S8T+D118K, S8T+T119R, S8T+S131T, S8T+E133R,S8T+E133Q, S8T+D135P, S8T+A136P, S8T+D139A, S8T+D139R, S8T+K142M,S8T+K142V, S8T+K142S, S8T+K142R, S8T+Q143R, S8T+N150T, S8T+N150R,S8T+N150S, S8T+Q169A, S8T+Q169R, S8T+Q169K, S8T+H172R, S8T+Y174R,S8T+Y174L, S8T+Y174W, S8T+Y174F, S8T+R176Q, S8T+E177S, S8T+E177Y,S8T+N180R, S8T+P183T, S8T+P183G, S8T+Q184E, S8T+Q184K, S8T+R185G,S8T+Y196W, S8T+Y196F, S8T+N200T, S8T+S202R, S8T+Q203T, S8T+R205K,S8T+R210L, S8T+R210G, S8T+R210M, S8T+N213V, S8T+N213D, S8T+T228S,S8T+N229D, S8T+E234F, S8T+E234Y, S8T+A235K, S8T+A235R, S8T+S241C,S8T+Q243K, S8T+Q243E, S8T+R244K, S8T+R244V, S8T+A250G, S8T+K254Y,S8T+G257W, S8T+G257E, S8T+G257A, S8T+W260F, S8T+W260Y, S8T+W260L,S8T+W260T, S8T+Y262F, S8T+S266A, S8T+D268N, S8T+A270D, S8T+N272M,S8T+N272T, S8T+N273E, S8T+N273D, S8T+A276E, S8T+A276W, S8T+A276D,S8T+N279D, S8T+N279E, S8T+T280L, S8T+N283W, S8T+N283H, S8T+Y286W,S8T+Y286F, S8T+L288I, S8T+E290A, S8T+L294P, S8T+L294K, S8T+L294I,S8T+L294R, S8T+L294V, S8T+L294H, S8T+S295K, S8T+S295V, S8T+S295P,S8T+S295L, S8T+S295R, S8T+S295A, S8T+S295N, S8T+S295M, S8T+S295I,S8T+T296S, S8T+F298Y, S8P+T11K, S8P+T11R, S8P+Y13F, S8P+D14S, S8P+D14K,S8P+N18V, S8P+N18R, S8P+A30T, S8P+Y32F, S8P+Y32W, S8P+K33Q, S8P+D34G,S8P+Q35L, S8P+T37P, S8P+E41V, S8P+E41N, S8P+N45G, S8P+G47S, S8P+G47A,S8P+D57N, S8P+G59Q, S8P+Q60R, S8P+K63R, S8P+K63Q, S8P+D65E, S8P+R70K,S8P+N71S, S8P+S74K, S8P+E77T, S8P+E77N, S8P+D78G, S8P+H80K, S8P+V82R,S8P+V82I, S8P+V82S, S8P+A83P, S8P+A83S, S8P+Y93Q, S8P+Y93A, S8P+S95D,S8P+A97R, S8P+S98P, S8P+S98D, S8P+N100Y, S8P+D104A, S8P+D104G,S8P+E108S, S8P+S111A, S8P+S111 K, S8P+S111 R, S8P+I114Q, S8P+I114M,S8P+I114W, S8P+K116R, S8P+D118K, S8P+T119R, S8P+S131T, S8P+E133R,S8P+E133Q, S8P+D135P, S8P+A136P, S8P+D139A, S8P+D139R, S8P+K142M,S8P+K142V, S8P+K142S, S8P+K142R, S8P+Q143R, S8P+N150T, S8P+N150R,S8P+N150S, S8P+Q169A, S8P+Q169R, S8P+Q169K, S8P+H172R, S8P+Y174R,S8P+Y174L, S8P+Y174W, S8P+Y174F, S8P+R176Q, S8P+E177S, S8P+E177Y,S8P+N180R, S8P+P183T, S8P+P183G, S8P+Q184E, S8P+Q184K, S8P+R185G,S8P+Y196W, S8P+Y196F, S8P+N200T, S8P+S202R, S8P+Q203T, S8P+R205K,S8P+R210L, S8P+R210G, S8P+R210M, S8P+N213V, S8P+N213D, S8P+T228S,S8P+N229D, S8P+E234F, S8P+E234Y, S8P+A235K, S8P+A235R, S8P+S241C,S8P+Q243K, S8P+Q243E, S8P+R244K, S8P+R244V, S8P+A250G, S8P+K254Y,S8P+G257W, S8P+G257E, S8P+G257A, S8P+W260F, S8P+W260Y, S8P+W260L,S8P+W260T, S8P+Y262F, S8P+S266A, S8P+D268N, S8P+A270D, S8P+N272M,S8P+N272T, S8P+N273E, S8P+N273D, S8P+A276E, S8P+A276W, S8P+A276D,S8P+N279D, S8P+N279E, S8P+T280L, S8P+N283W, S8P+N283H, S8P+Y286W,S8P+Y286F, S8P+L288I, S8P+E290A, S8P+L294P, S8P+L294K, S8P+L294I,S8P+L294R, S8P+L294V, S8P+L294H, S8P+S295K, S8P+S295V, S8P+S295P,S8P+S295L, S8P+S295R, S8P+S295A, S8P+S295N, S8P+S295M, S8P+S295I,S8P+T296S, S8P+F298Y, S8R+T11K, S8R+T11R, S8R+Y13F, S8R+D14S, S8R+D14K,S8R+N18V, S8R+N18R, S8R+A30T, S8R+Y32F, S8R+Y32W, S8R+K33Q, S8R+D34G,S8R+Q35L, S8R+T37P, S8R+E41V, S8R+E41N, S8R+N45G, S8R+G47S, S8R+G47A,S8R+D57N, S8R+G59Q, S8R+Q60R, S8R+K63R, S8R+K63Q, S8R+D65E, S8R+R70K,S8R+N71S, S8R+S74K, S8R+E77T, S8R+E77N, S8R+D78G, S8R+H80K, S8R+V82R,S8R+V82I, S8R+V82S, S8R+A83P, S8R+A83S, S8R+Y93Q, S8R+Y93A, S8R+S95D,S8R+A97R, S8R+S98P, S8R+S98D, S8R+N100Y, S8R+D104A, S8R+D104G,S8R+E108S, S8R+S111A, S8R+S111K, S8R+S111R, S8R+I114Q, S8R+I114M,S8R+I114W, S8R+K116R, S8R+D118K, S8R+T119R, S8R+S131T, S8R+E133R,S8R+E133Q, S8R+D135P, S8R+A136P, S8R+D139A, S8R+D139R, S8R+K142M,S8R+K142V, S8R+K142S, S8R+K142R, S8R+Q143R, S8R+N150T, S8R+N150R,S8R+N150S, S8R+Q169A, S8R+Q169R, S8R+Q169K, S8R+H172R, S8R+Y174R,S8R+Y174L, S8R+Y174W, S8R+Y174F, S8R+R176Q, S8R+E177S, S8R+E177Y,S8R+N180R, S8R+P183T, S8R+P183G, S8R+Q184E, S8R+Q184K, S8R+R185G,S8R+Y196W, S8R+Y196F, S8R+N200T, S8R+S202R, S8R+Q203T, S8R+R205K,S8R+R210L, S8R+R210G, S8R+R210M, S8R+N213V, S8R+N213D, S8R+T228S,S8R+N229D, S8R+E234F, S8R+E234Y, S8R+A235K, S8R+A235R, S8R+S241C,S8R+Q243K, S8R+Q243E, S8R+R244K, S8R+R244V, S8R+A250G, S8R+K254Y,S8R+G257W, S8R+G257E, S8R+G257A, S8R+W260F, S8R+W260Y, S8R+W260L,S8R+W260T, S8R+Y262F, S8R+S266A, S8R+D268N, S8R+A270D, S8R+N272M,S8R+N272T, S8R+N273E, S8R+N273D, S8R+A276E, S8R+A276W, S8R+A276D,S8R+N279D, S8R+N279E, S8R+T280L, S8R+N283W, S8R+N283H, S8R+Y286W,S8R+Y286F, S8R+L288I, S8R+E290A, S8R+L294P, S8R+L294K, S8R+L294I,S8R+L294R, S8R+L294V, S8R+L294H, S8R+S295K, S8R+S295V, S8R+S295P,S8R+S295L, S8R+S295R, S8R+S295A, S8R+S295N, S8R+S295M, S8R+S295I,S8R+T296S, S8R+F298Y, T11K+Y13F, T11K+D14S, T11K+D14K, T11K+N18V,T11K+N18R, T11K+A30T, T11K+Y32F, T11K+Y32W, T11K+K33Q, T11K+D34G,T11K+Q35L, T11K+T37P, T11K+E41V, T11K+E41N, T11K+N45G, T11K+G47S,T11K+G47A, T11K+D57N, T11K+G59Q, T11K+Q60R, T11K+K63R, T11K+K63Q,T11K+D65E, T11K+R70K, T11K+N71S, T11K+S74K, T11K+E77T, T11K+E77N,T11K+D78G, T11K+H80K, T11K+V82R, T11K+V82I, T11K+V82S, T11K+A83P,T11K+A83S, T11K+Y93Q, T11K+Y93A, T11K+S95D, T11K+A97R, T11K+S98P,T11K+S98D, T11K+N100Y, T11K+D104A, T11K+D104G, T11K+E108S, T11K+S111A,T11K+S111K, T11K+S111R, T11K+I114Q, T11K+I114M, T11K+I114W, T11K+K116R,T11K+D118K, T11K+T119R, T11K+S131T, T11K+E133R, T11K+E133Q, T11K+D135P,T11K+A136P, T11K+D139A, T11K+D139R, T11K+K142M, T11K+K142V, T11K+K142S,T11K+K142R, T11K+Q143R, T11K+N150T, T11K+N150R, T11K+N150S, T11K+Q169A,T11K+Q169R, T11K+Q169K, T11K+H172R, T11K+Y174R, T11K+Y174L, T11K+Y174W,T11K+Y174F, T11K+R176Q, T11K+E177S, T11K+E177Y, T11K+N180R, T11K+P183T,T11K+P183G, T11K+Q184E, T11K+Q184K, T11K+R185G, T11K+Y196W, T11K+Y196F,T11K+N200T, T11K+S202R, T11K+Q203T, T11K+R205K, T11K+R210L, T11K+R210G,T11K+R210M, T11K+N213V, T11K+N213D, T11K+T228S, T11K+N229D, T11K+E234F,T11K+E234Y, T11K+A235K, T11K+A235R, T11K+S241C, T11K+Q243K, T11K+Q243E,T11K+R244K, T11K+R244V, T11K+A250G, T11K+K254Y, T11K+G257W, T11K+G257E,T11K+G257A, T11K+W260F, T11K+W260Y, T11K+W260L, T11K+W260T, T11K+Y262F,T11K+S266A, T11K+D268N, T11K+A270D, T11K+N272M, T11K+N272T, T11K+N273E,T11K+N273D, T11K+A276E, T11K+A276W, T11K+A276D, T11K+N279D, T11K+N279E,T11K+T280L, T11K+N283W, T11K+N283H, T11K+Y286W, T11K+Y286F, T11K+L288I,T11K+E290A, T11K+L294P, T11K+L294K, T11K+L294I, T11K+L294R, T11K+L294V,T11K+L294H, T11K+S295K, T11K+S295V, T11K+S295P, T11K+S295L, T11K+S295R,T11K+S295A, T11K+S295N, T11K+S295M, T11K+S295I, T11K+T296S, T11K+F298Y,T11R+Y13F, T11R+D14S, T11R+D14K, T11R+N18V, T11R+N18R, T11R+A30T,T11R+Y32F, T11R+Y32W, T11R+K33Q, T11R+D34G, T11R+Q35L, T11R+T37P,T11R+E41V, T11R+E41N, T11R+N45G, T11R+G47S, T11R+G47A, T11R+D57N,T11R+G59Q, T11R+Q60R, T11R+K63R, T11R+K63Q, T11R+D65E, T11R+R70K,T11R+N71S, T11R+S74K, T11R+E77T, T11R+E77N, T11R+D78G, T11R+H80K,T11R+V82R, T11R+V82I, T11R+V82S, T11R+A83P, T11R+A83S, T11R+Y93Q,T11R+Y93A, T11R+S95D, T11R+A97R, T11R+S98P, T11R+S98D, T11R+N100Y,T11R+D104A, T11R+D104G, T11R+E108S, T11R+S111A, T11R+S111K, T11R+S111R,T11R+I114Q, T11R+I114M, T11R+I114W, T11R+K116R, T11R+D118K, T11R+T119R,T11R+S131T, T11R+E133R, T11R+E133Q, T11R+D135P, T11R+A136P, T11R+D139A,T11R+D139R, T11R+K142M, T11R+K142V, T11R+K142S, T11R+K142R, T11R+Q143R,T11R+N150T, T11R+N150R, T11R+N150S, T11R+Q169A, T11R+Q169R, T11R+Q169K,T11R+H172R, T11R+Y174R, T11R+Y174L, T11R+Y174W, T11R+Y174F, T11R+R176Q,T11R+E177S, T11R+E177Y, T11R+N180R, T11R+P183T, T11R+P183G, T11R+Q184E,T11R+Q184K, T11R+R185G, T11R+Y196W, T11R+Y196F, T11R+N200T, T11R+S202R,T11R+Q203T, T11R+R205K, T11R+R210L, T11R+R210G, T11R+R210M, T11R+N213V,T11R+N213D, T11R+T228S, T11R+N229D, T11R+E234F, T11R+E234Y, T11R+A235K,T11R+A235R, T11R+S241C, T11R+Q243K, T11R+Q243E, T11R+R244K, T11R+R244V,T11R+A250G, T11R+K254Y, T11R+G257W, T11R+G257E, T11R+G257A, T11R+W260F,T11R+W260Y, T11R+W260L, T11R+W260T, T11R+Y262F, T11R+S266A, T11R+D268N,T11R+A270D, T11R+N272M, T11R+N272T, T11R+N273E, T11R+N273D, T11R+A276E,T11R+A276W, T11R+A276D, T11R+N279D, T11R+N279E, T11R+T280L, T11R+N283W,T11R+N283H, T11R+Y286W, T11R+Y286F, T11R+L288I, T11R+E290A, T11R+L294P,T11R+L294K, T11R+L294I, T11R+L294R, T11R+L294V, T11R+L294H, T11R+S295K,T11R+S295V, T11R+S295P, T11R+S295L, T11R+S295R, T11R+S295A, T11R+S295N,T11R+S295M, T11R+S295I, T11R+T296S, T11R+F298Y, Y13F+D14S, Y13F+D14K,Y13F+N18V, Y13F+N18R, Y13F+A30T, Y13F+Y32F, Y13F+Y32W, Y13F+K33Q,Y13F+D34G, Y13F+Q35L, Y13F+T37P, Y13F+E41V, Y13F+E41N, Y13F+N45G,Y13F+G47S, Y13F+G47A, Y13F+D57N, Y13F+G59Q, Y13F+Q60R, Y13F+K63R,Y13F+K63Q, Y13F+D65E, Y13F+R70K, Y13F+N71S, Y13F+S74K, Y13F+E77T,Y13F+E77N, Y13F+D78G, Y13F+H80K, Y13F+V82R, Y13F+V82I, Y13F+V82S,Y13F+A83P, Y13F+A83S, Y13F+Y93Q, Y13F+Y93A, Y13F+S95D, Y13F+A97R,Y13F+S98P, Y13F+S98D, Y13F+N100Y, Y13F+D104A, Y13F+D104G, Y13F+E108S,Y13F+S111A, Y13F+S111K, Y13F+S111R, Y13F+I114Q, Y13F+I114M, Y13F+I114W,Y13F+K116R, Y13F+D118K, Y13F+T119R, Y13F+S131T, Y13F+E133R, Y13F+E133Q,Y13F+D135P, Y13F+A136P, Y13F+D139A, Y13F+D139R, Y13F+K142M, Y13F+K142V,Y13F+K142S, Y13F+K142R, Y13F+Q143R, Y13F+N150T, Y13F+N150R, Y13F+N150S,Y13F+Q169A, Y13F+Q169R, Y13F+Q169K, Y13F+H172R, Y13F+Y174R, Y13F+Y174L,Y13F+Y174W, Y13F+Y174F, Y13F+R176Q, Y13F+E177S, Y13F+E177Y, Y13F+N180R,Y13F+P183T, Y13F+P183G, Y13F+Q184E, Y13F+Q184K, Y13F+R185G, Y13F+Y196W,Y13F+Y196F, Y13F+N200T, Y13F+S202R, Y13F+Q203T, Y13F+R205K, Y13F+R210L,Y13F+R210G, Y13F+R210M, Y13F+N213V, Y13F+N213D, Y13F+T228S, Y13F+N229D,Y13F+E234F, Y13F+E234Y, Y13F+A235K, Y13F+A235R, Y13F+S241C, Y13F+Q243K,Y13F+Q243E, Y13F+R244K, Y13F+R244V, Y13F+A250G, Y13F+K254Y, Y13F+G257W,Y13F+G257E, Y13F+G257A, Y13F+W260F, Y13F+W260Y, Y13F+W260L, Y13F+W260T,Y13F+Y262F, Y13F+S266A, Y13F+D268N, Y13F+A270D, Y13F+N272M, Y13F+N272T,Y13F+N273E, Y13F+N273D, Y13F+A276E, Y13F+A276W, Y13F+A276D, Y13F+N279D,Y13F+N279E, Y13F+T280L, Y13F+N283W, Y13F+N283H, Y13F+Y286W, Y13F+Y286F,Y13F+L288I, Y13F+E290A, Y13F+L294P, Y13F+L294K, Y13F+L294I, Y13F+L294R,Y13F+L294V, Y13F+L294H, Y13F+S295K, Y13F+S295V, Y13F+S295P, Y13F+S295L,Y13F+S295R, Y13F+S295A, Y13F+S295N, Y13F+S295M, Y13F+S295I, Y13F+T296S,Y13F+F298Y, D14S+N18V, D14S+N18R, D14S+A30T, D14S+Y32F, D14S+Y32W,D14S+K33Q, D14S+D34G, D14S+Q35L, D14S+T37P, D14S+E41V, D14S+E41N,D14S+N45G, D14S+G47S, D14S+G47A, D14S+D57N, D14S+G59Q, D14S+Q60R,D14S+K63R, D14S+K63Q, D14S+D65E, D14S+R70K, D14S+N71S, D14S+S74K,D14S+E77T, D14S+E77N, D14S+D78G, D14S+H80K, D14S+V82R, D14S+V82I,D14S+V82S, D14S+A83P, D14S+A83S, D14S+Y93Q, D14S+Y93A, D14S+S95D,D14S+A97R, D14S+S98P, D14S+S98D, D14S+N100Y, D14S+D104A, D14S+D104G,D14S+E108S, D14S+S111A, D14S+S111K, D14S+S111R, D14S+I114Q, D14S+I114M,D14S+I114W, D14S+K116R, D14S+D118K, D14S+T119R, D14S+S131T, D14S+E133R,D14S+E133Q, D14S+D135P, D14S+A136P, D14S+D139A, D14S+D139R, D14S+K142M,D14S+K142V, D14S+K142S, D14S+K142R, D14S+Q143R, D14S+N150T, D14S+N150R,D14S+N150S, D14S+Q169A, D14S+Q169R, D14S+Q169K, D14S+H172R, D14S+Y174R,D14S+Y174L, D14S+Y174W, D14S+Y174F, D14S+R176Q, D14S+E177S, D14S+E177Y,D14S+N180R, D14S+P183T, D14S+P183G, D14S+Q184E, D14S+Q184K, D14S+R185G,D14S+Y196W, D14S+Y196F, D14S+N200T, D14S+S202R, D14S+Q203T, D14S+R205K,D14S+R210L, D14S+R210G, D14S+R210M, D14S+N213V, D14S+N213D, D14S+T228S,D14S+N229D, D14S+E234F, D14S+E234Y, D14S+A235K, D14S+A235R, D14S+S241C,D14S+Q243K, D14S+Q243E, D14S+R244K, D14S+R244V, D14S+A250G, D14S+K254Y,D14S+G257W, D14S+G257E, D14S+G257A, D14S+W260F, D14S+W260Y, D14S+W260L,D14S+W260T, D14S+Y262F, D14S+S266A, D14S+D268N, D14S+A270D, D14S+N272M,D14S+N272T, D14S+N273E, D14S+N273D, D14S+A276E, D14S+A276W, D14S+A276D,D14S+N279D, D14S+N279E, D14S+T280L, D14S+N283W, D14S+N283H, D14S+Y286W,D14S+Y286F, D14S+L288I, D14S+E290A, D14S+L294P, D14S+L294K, D14S+L294I,D14S+L294R, D14S+L294V, D14S+L294H, D14S+S295K, D14S+S295V, D14S+S295P,D14S+S295L, D14S+S295R, D14S+S295A, D14S+S295N, D14S+S295M, D14S+S295I,D14S+T296S, D14S+F298Y, D14K+N18V, D14K+N18R, D14K+A30T, D14K+Y32F,D14K+Y32W, D14K+K33Q, D14K+D34G, D14K+Q35L, D14K+T37P, D14K+E41V,D14K+E41N, D14K+N45G, D14K+G47S, D14K+G47A, D14K+D57N, D14K+G59Q,D14K+Q60R, D14K+K63R, D14K+K63Q, D14K+D65E, D14K+R70K, D14K+N71S,D14K+S74K, D14K+E77T, D14K+E77N, D14K+D78G, D14K+H80K, D14K+V82R,D14K+V82I, D14K+V82S, D14K+A83P, D14K+A83S, D14K+Y93Q, D14K+Y93A,D14K+S95D, D14K+A97R, D14K+S98P, D14K+S98D, D14K+N100Y, D14K+D104A,D14K+D104G, D14K+E108S, D14K+S111A, D14K+S111K, D14K+S111R, D14K+I114Q,D14K+I114M, D14K+I114W, D14K+K116R, D14K+D118K, D14K+T119R, D14K+S131T,D14K+E133R, D14K+E133Q, D14K+D135P, D14K+A136P, D14K+D139A, D14K+D139R,D14K+K142M, D14K+K142V, D14K+K142S, D14K+K142R, D14K+Q143R, D14K+N150T,D14K+N150R, D14K+N150S, D14K+Q169A, D14K+Q169R, D14K+Q169K, D14K+H172R,D14K+Y174R, D14K+Y174L, D14K+Y174W, D14K+Y174F, D14K+R176Q, D14K+E177S,D14K+E177Y, D14K+N180R, D14K+P183T, D14K+P183G, D14K+Q184E, D14K+Q184K,D14K+R185G, D14K+Y196W, D14K+Y196F, D14K+N200T, D14K+S202R, D14K+Q203T,D14K+R205K, D14K+R210L, D14K+R210G, D14K+R210M, D14K+N213V, D14K+N213D,D14K+T228S, D14K+N229D, D14K+E234F, D14K+E234Y, D14K+A235K, D14K+A235R,D14K+S241C, D14K+Q243K, D14K+Q243E, D14K+R244K, D14K+R244V, D14K+A250G,D14K+K254Y, D14K+G257W, D14K+G257E, D14K+G257A, D14K+W260F, D14K+W260Y,D14K+W260L, D14K+W260T, D14K+Y262F, D14K+S266A, D14K+D268N, D14K+A270D,D14K+N272M, D14K+N272T, D14K+N273E, D14K+N273D, D14K+A276E, D14K+A276W,D14K+A276D, D14K+N279D, D14K+N279E, D14K+T280L, D14K+N283W, D14K+N283H,D14K+Y286W, D14K+Y286F, D14K+L288I, D14K+E290A, D14K+L294P, D14K+L294K,D14K+L294I, D14K+L294R, D14K+L294V, D14K+L294H, D14K+S295K, D14K+S295V,D14K+S295P, D14K+S295L, D14K+S295R, D14K+S295A, D14K+S295N, D14K+S295M,D14K+S295I, D14K+T296S, D14K+F298Y, N18V+A30T, N18V+Y32F, N18V+Y32W,N18V+K33Q, N18V+D34G, N18V+Q35L, N18V+T37P, N18V+E41V, N18V+E41N,N18V+N45G, N18V+G47S, N18V+G47A, N18V+D57N, N18V+G59Q, N18V+Q60R,N18V+K63R, N18V+K63Q, N18V+D65E, N18V+R70K, N18V+N71S, N18V+S74K,N18V+E77T, N18V+E77N, N18V+D78G, N18V+H80K, N18V+V82R, N18V+V82I,N18V+V82S, N18V+A83P, N18V+A83S, N18V+Y93Q, N18V+Y93A, N18V+S95D,N18V+A97R, N18V+S98P, N18V+S98D, N18V+N100Y, N18V+D104A, N18V+D104G,N18V+E108S, N18V+S111A, N18V+S111K, N18V+S111R, N18V+I114Q, N18V+I114M,N18V+I114W, N18V+K116R, N18V+D118K, N18V+T119R, N18V+S131T, N18V+E133R,N18V+E133Q, N18V+D135P, N18V+A136P, N18V+D139A, N18V+D139R, N18V+K142M,N18V+K142V, N18V+K142S, N18V+K142R, N18V+Q143R, N18V+N150T, N18V+N150R,N18V+N150S, N18V+Q169A, N18V+Q169R, N18V+Q169K, N18V+H172R, N18V+Y174R,N18V+Y174L, N18V+Y174W, N18V+Y174F, N18V+R176Q, N18V+E177S, N18V+E177Y,N18V+N180R, N18V+P183T, N18V+P183G, N18V+Q184E, N18V+Q184K, N18V+R185G,N18V+Y196W, N18V+Y196F, N18V+N200T, N18V+S202R, N18V+Q203T, N18V+R205K,N18V+R210L, N18V+R210G, N18V+R210M, N18V+N213V, N18V+N213D, N18V+T228S,N18V+N229D, N18V+E234F, N18V+E234Y, N18V+A235K, N18V+A235R, N18V+S241C,N18V+Q243K, N18V+Q243E, N18V+R244K, N18V+R244V, N18V+A250G, N18V+K254Y,N18V+G257W, N18V+G257E, N18V+G257A, N18V+W260F, N18V+W260Y, N18V+W260L,N18V+W260T, N18V+Y262F, N18V+S266A, N 18V+D268N, N18V+A270D, N18V+N272M,N18V+N272T, N18V+N273E, N18V+N273D, N18V+A276E, N18V+A276W, N18V+A276D,N18V+N279D, N18V+N279E, N18V+T280L, N18V+N283W, N18V+N283H, N18V+Y286W,N18V+Y286F, N18V+L288I, N18V+E290A, N18V+L294P, N18V+L294K, N18V+L294I,N18V+L294R, N18V+L294V, N18V+L294H, N18V+S295K, N18V+S295V, N18V+S295P,N18V+S295L, N18V+S295R, N18V+S295A, N18V+S295N, N18V+S295M, N18V+S295I,N18V+T296S, N 18V+F298Y, N18R+A30T, N18R+Y32F, N18R+Y32W, N18R+K33Q,N18R+D34G, N18R+Q35L, N18R+T37P, N18R+E41V, N18R+E41 N, N18R+N45G,N18R+G47S, N18R+G47A, N18R+D57N, N18R+G59Q, N18R+Q60R, N18R+K63R,N18R+K63Q, N18R+D65E, N18R+R70K, N18R+N71S, N18R+S74K, N18R+E77T,N18R+E77N, N18R+D78G, N18R+H80K, N18R+V82R, N18R+V82I, N18R+V82S,N18R+A83P, N18R+A83S, N18R+Y93Q, N18R+Y93A, N18R+S95D, N18R+A97R,N18R+S98P, N18R+S98D, N18R+N100Y, N18R+D104A, N18R+D104G, N18R+E108S,N18R+S111A, N18R+S111K, N18R+S111R, N18R+I114Q, N18R+I114M, N18R+I114W,N18R+K116R, N18R+D118K, N18R+T119R, N18R+S131T, N18R+E133R, N18R+E133Q,N18R+D135P, N18R+A136P, N18R+D139A, N18R+D139R, N18R+K142M, N18R+K142V,N18R+K142S, N18R+K142R, N18R+Q143R, N18R+N150T, N18R+N150R, N18R+N150S,N18R+Q169A, N18R+Q169R, N18R+Q169K, N18R+H172R, N18R+Y174R, N18R+Y174L,N18R+Y174W, N18R+Y174F, N18R+R176Q, N18R+E177S, N18R+E177Y, N18R+N180R,N18R+P183T, N18R+P183G, N18R+Q184E, N18R+Q184K, N18R+R185G, N18R+Y196W,N18R+Y196F, N18R+N200T, N18R+S202R, N18R+Q203T, N18R+R205K, N18R+R210L,N18R+R210G, N18R+R210M, N18R+N213V, N18R+N213D, N18R+T228S, N18R+N229D,N18R+E234F, N18R+E234Y, N18R+A235K, N18R+A235R, N18R+S241C, N18R+Q243K,N18R+Q243E, N18R+R244K, N18R+R244V, N18R+A250G, N18R+K254Y, N18R+G257W,N18R+G257E, N18R+G257A, N18R+W260F, N18R+W260Y, N18R+W260L, N18R+W260T,N18R+Y262F, N18R+S266A, N18R+D268N, N18R+A270D, N18R+N272M, N18R+N272T,N18R+N273E, N18R+N273D, N18R+A276E, N18R+A276W, N18R+A276D, N18R+N279D,N18R+N279E, N18R+T280L, N18R+N283W, N18R+N283H, N18R+Y286W, N18R+Y286F,N18R+L288I, N18R+E290A, N18R+L294P, N18R+L294K, N18R+L294I, N18R+L294R,N18R+L294V, N18R+L294H, N18R+S295K, N18R+S295V, N18R+S295P, N18R+S295L,N18R+S295R, N18R+S295A, N18R+S295N, N18R+S295M, N18R+S295I, N18R+T296S,N18R+F298Y, A30T+Y32F, A30T+Y32W, A30T+K33Q, A30T+D34G, A30T+Q35L,A30T+T37P, A30T+E41V, A30T+E41N, A30T+N45G, A30T+G47S, A30T+G47A,A30T+D57N, A30T+G59Q, A30T+Q60R, A30T+K63R, A30T+K63Q, A30T+D65E,A30T+R70K, A30T+N71S, A30T+S74K, A30T+E77T, A30T+E77N, A30T+D78G,A30T+H80K, A30T+V82R, A30T+V82I, A30T+V82S, A30T+A83P, A30T+A83S,A30T+Y93Q, A30T+Y93A, A30T+S95D, A30T+A97R, A30T+S98P, A30T+S98D,A30T+N100Y, A30T+D104A, A30T+D104G, A30T+E108S, A30T+S111A, A30T+S111K,A30T+S111R, A30T+I114Q, A30T+I114M, A30T+I114W, A30T+K116R, A30T+D118K,A30T+T119R, A30T+S131T, A30T+E133R, A30T+E133Q, A30T+D135P, A30T+A136P,A30T+D139A, A30T+D139R, A30T+K142M, A30T+K142V, A30T+K142S, A30T+K142R,A30T+Q143R, A30T+N150T, A30T+N 150R, A30T+N150S, A30T+Q169A, A30T+Q169R,A30T+Q169K, A30T+H172R, A30T+Y174R, A30T+Y174L, A30T+Y174W, A30T+Y174F,A30T+R176Q, A30T+E177S, A30T+E177Y, A30T+N180R, A30T+P183T, A30T+P183G,A30T+Q184E, A30T+Q184K, A30T+R185G, A30T+Y196W, A30T+Y196F, A30T+N200T,A30T+S202R, A30T+Q203T, A30T+R205K, A30T+R210L, A30T+R210G, A30T+R210M,A30T+N213V, A30T+N213D, A30T+T228S, A30T+N229D, A30T+E234F, A30T+E234Y,A30T+A235K, A30T+A235R, A30T+S241C, A30T+Q243K, A30T+Q243E, A30T+R244K,A30T+R244V, A30T+A250G, A30T+K254Y, A30T+G257W, A30T+G257E, A30T+G257A,A30T+W260F, A30T+W260Y, A30T+W260L, A30T+W260T, A30T+Y262F, A30T+S266A,A30T+D268N, A30T+A270D, A30T+N272M, A30T+N272T, A30T+N273E, A30T+N273D,A30T+A276E, A30T+A276W, A30T+A276D, A30T+N279D, A30T+N279E, A30T+T280L,A30T+N283W, A30T+N283H, A30T+Y286W, A30T+Y286F, A30T+L288I, A30T+E290A,A30T+L294P, A30T+L294K, A30T+L294I, A30T+L294R, A30T+L294V, A30T+L294H,A30T+S295K, A30T+S295V, A30T+S295P, A30T+S295L, A30T+S295R, A30T+S295A,A30T+S295N, A30T+S295M, A30T+S295I, A30T+T296S, A30T+F298Y, Y32F+K33Q,Y32F+D34G, Y32F+Q35L, Y32F+T37P, Y32F+E41V, Y32F+E41N, Y32F+N45G,Y32F+G47S, Y32F+G47A, Y32F+D57N, Y32F+G59Q, Y32F+Q60R, Y32F+K63R,Y32F+K63Q, Y32F+D65E, Y32F+R70K, Y32F+N71S, Y32F+S74K, Y32F+E77T,Y32F+E77N, Y32F+D78G, Y32F+H80K, Y32F+V82R, Y32F+V82I, Y32F+V82S,Y32F+A83P, Y32F+A83S, Y32F+Y93Q, Y32F+Y93A, Y32F+S95D, Y32F+A97R,Y32F+S98P, Y32F+S98D, Y32F+N100Y, Y32F+D104A, Y32F+D104G, Y32F+E108S,Y32F+S111A, Y32F+S111K, Y32F+S111R, Y32F+I114Q, Y32F+I114M, Y32F+I114W,Y32F+K116R, Y32F+D118K, Y32F+T119R, Y32F+S131T, Y32F+E133R, Y32F+E133Q,Y32F+D135P, Y32F+A136P, Y32F+D139A, Y32F+D139R, Y32F+K142M, Y32F+K142V,Y32F+K142S, Y32F+K142R, Y32F+Q143R, Y32F+N150T, Y32F+N 150R, Y32F+N150S,Y32F+Q169A, Y32F+Q169R, Y32F+Q169K, Y32F+H172R, Y32F+Y174R, Y32F+Y174L,Y32F+Y174W, Y32F+Y174F, Y32F+R176Q, Y32F+E177S, Y32F+E177Y, Y32F+N180R,Y32F+P183T, Y32F+P183G, Y32F+Q184E, Y32F+Q184K, Y32F+R185G, Y32F+Y196W,Y32F+Y196F, Y32F+N200T, Y32F+S202R, Y32F+Q203T, Y32F+R205K, Y32F+R210L,Y32F+R210G, Y32F+R210M, Y32F+N213V, Y32F+N213D, Y32F+T228S, Y32F+N229D,Y32F+E234F, Y32F+E234Y, Y32F+A235K, Y32F+A235R, Y32F+S241C, Y32F+Q243K,Y32F+Q243E, Y32F+R244K, Y32F+R244V, Y32F+A250G, Y32F+K254Y, Y32F+G257W,Y32F+G257E, Y32F+G257A, Y32F+W260F, Y32F+W260Y, Y32F+W260L, Y32F+W260T,Y32F+Y262F, Y32F+S266A, Y32F+D268N, Y32F+A270D, Y32F+N272M, Y32F+N272T,Y32F+N273E, Y32F+N273D, Y32F+A276E, Y32F+A276W, Y32F+A276D, Y32F+N279D,Y32F+N279E, Y32F+T280L, Y32F+N283W, Y32F+N283H, Y32F+Y286W, Y32F+Y286F,Y32F+L288I, Y32F+E290A, Y32F+L294P, Y32F+L294K, Y32F+L294I, Y32F+L294R,Y32F+L294V, Y32F+L294H, Y32F+S295K, Y32F+S295V, Y32F+S295P, Y32F+S295L,Y32F+S295R, Y32F+S295A, Y32F+S295N, Y32F+S295M, Y32F+S295I, Y32F+T296S,Y32F+F298Y, Y32W+K33Q, Y32W+D34G, Y32W+Q35L, Y32W+T37P, Y32W+E41V,Y32W+E41N, Y32W+N45G, Y32W+G47S, Y32W+G47A, Y32W+D57N, Y32W+G59Q,Y32W+Q60R, Y32W+K63R, Y32W+K63Q, Y32W+D65E, Y32W+R70K, Y32W+N71S,Y32W+S74K, Y32W+E77T, Y32W+E77N, Y32W+D78G, Y32W+H80K, Y32W+V82R,Y32W+V82I, Y32W+V82S, Y32W+A83P, Y32W+A83S, Y32W+Y93Q, Y32W+Y93A,Y32W+S95D, Y32W+A97R, Y32W+S98P, Y32W+S98D, Y32W+N100Y, Y32W+D104A,Y32W+D104G, Y32W+E108S, Y32W+S111A, Y32W+S111K, Y32W+S111R, Y32W+I114Q,Y32W+I114M, Y32W+I114W, Y32W+K116R, Y32W+D118K, Y32W+T119R, Y32W+S131T,Y32W+E133R, Y32W+E133Q, Y32W+D135P, Y32W+A136P, Y32W+D139A, Y32W+D139R,Y32W+K142M, Y32W+K142V, Y32W+K142S, Y32W+K142R, Y32W+Q143R, Y32W+N150T,Y32W+N150R, Y32W+N150S, Y32W+Q169A, Y32W+Q169R, Y32W+Q169K, Y32W+H 172R,Y32W+Y174R, Y32W+Y174L, Y32W+Y174W, Y32W+Y174F, Y32W+R176Q, Y32W+E177S,Y32W+E177Y, Y32W+N180R, Y32W+P183T, Y32W+P183G, Y32W+Q184E, Y32W+Q184K,Y32W+R185G, Y32W+Y196W, Y32W+Y196F, Y32W+N200T, Y32W+S202R, Y32W+Q203T,Y32W+R205K, Y32W+R210L, Y32W+R210G, Y32W+R210M, Y32W+N213V, Y32W+N213D,Y32W+T228S, Y32W+N229D, Y32W+E234F, Y32W+E234Y, Y32W+A235K, Y32W+A235R,Y32W+S241C, Y32W+Q243K, Y32W+Q243E, Y32W+R244K, Y32W+R244V, Y32W+A250G,Y32W+K254Y, Y32W+G257W, Y32W+G257E, Y32W+G257A, Y32W+W260F, Y32W+W260Y,Y32W+W260L, Y32W+W260T, Y32W+Y262F, Y32W+S266A, Y32W+D268N, Y32W+A270D,Y32W+N272M, Y32W+N272T, Y32W+N273E, Y32W+N273D, Y32W+A276E, Y32W+A276W,Y32W+A276D, Y32W+N279D, Y32W+N279E, Y32W+T280L, Y32W+N283W, Y32W+N283H,Y32W+Y286W, Y32W+Y286F, Y32W+L288I, Y32W+E290A, Y32W+L294P, Y32W+L294K,Y32W+L294I, Y32W+L294R, Y32W+L294V, Y32W+L294H, Y32W+S295K, Y32W+S295V,Y32W+S295P, Y32W+S295L, Y32W+S295R, Y32W+S295A, Y32W+S295N, Y32W+S295M,Y32W+S295I, Y32W+T296S, Y32W+F298Y, K33Q+D34G, K33Q+Q35L, K33Q+T37P,K33Q+E41V, K33Q+E41N, K33Q+N45G, K33Q+G47S, K33Q+G47A, K33Q+D57N,K33Q+G59Q, K33Q+Q60R, K33Q+K63R, K33Q+K63Q, K33Q+D65E, K33Q+R70K,K33Q+N71S, K33Q+S74K, K33Q+E77T, K33Q+E77N, K33Q+D78G, K33Q+H80K,K33Q+V82R, K33Q+V82I, K33Q+V82S, K33Q+A83P, K33Q+A83S, K33Q+Y93Q,K33Q+Y93A, K33Q+S95D, K33Q+A97R, K33Q+S98P, K33Q+S98D, K33Q+N100Y,K33Q+D104A, K33Q+D104G, K33Q+E108S, K33Q+S111A, K33Q+S111K, K33Q+S111R,K33Q+I114Q, K33Q+I114M, K33Q+I114W, K33Q+K116R, K33Q+D118K, K33Q+T119R,K33Q+S131T, K33Q+E133R, K33Q+E133Q, K33Q+D135P, K33Q+A136P, K33Q+D139A,K33Q+D139R, K33Q+K142M, K33Q+K142V, K33Q+K142S, K33Q+K142R, K33Q+Q143R,K33Q+N150T, K33Q+N150R, K33Q+N150S, K33Q+Q169A, K33Q+Q169R, K33Q+Q169K,K33Q+H172R, K33Q+Y174R, K33Q+Y174L, K33Q+Y174W, K33Q+Y174F, K33Q+R176Q,K33Q+E177S, K33Q+E177Y, K33Q+N180R, K33Q+P183T, K33Q+P183G, K33Q+Q184E,K33Q+Q184K, K33Q+R185G, K33Q+Y196W, K33Q+Y196F, K33Q+N200T, K33Q+S202R,K33Q+Q203T, K33Q+R205K, K33Q+R210L, K33Q+R210G, K33Q+R210M, K33Q+N213V,K33Q+N213D, K33Q+T228S, K33Q+N229D, K33Q+E234F, K33Q+E234Y, K33Q+A235K,K33Q+A235R, K33Q+S241C, K33Q+Q243K, K33Q+Q243E, K33Q+R244K, K33Q+R244V,K33Q+A250G, K33Q+K254Y, K33Q+G257W, K33Q+G257E, K33Q+G257A, K33Q+W260F,K33Q+W260Y, K33Q+W260L, K33Q+W260T, K33Q+Y262F, K33Q+S266A, K33Q+D268N,K33Q+A270D, K33Q+N272M, K33Q+N272T, K33Q+N273E, K33Q+N273D, K33Q+A276E,K33Q+A276W, K33Q+A276D, K33Q+N279D, K33Q+N279E, K33Q+T280L, K33Q+N283W,K33Q+N283H, K33Q+Y286W, K33Q+Y286F, K33Q+L288I, K33Q+E290A, K33Q+L294P,K33Q+L294K, K33Q+L294I, K33Q+L294R, K33Q+L294V, K33Q+L294H, K33Q+S295K,K33Q+S295V, K33Q+S295P, K33Q+S295L, K33Q+S295R, K33Q+S295A, K33Q+S295N,K33Q+S295M, K33Q+S295I, K33Q+T296S, K33Q+F298Y, D34G+Q35L, D34G+T37P,D34G+E41V, D34G+E41N, D34G+N45G, D34G+G47S, D34G+G47A, D34G+D57N,D34G+G59Q, D34G+Q60R, D34G+K63R, D34G+K63Q, D34G+D65E, D34G+R70K,D34G+N71S, D34G+S74K, D34G+E77T, D34G+E77N, D34G+D78G, D34G+H80K,D34G+V82R, D34G+V82I, D34G+V82S, D34G+A83P, D34G+A83S, D34G+Y93Q,D34G+Y93A, D34G+S95D, D34G+A97R, D34G+S98P, D34G+S98D, D34G+N100Y,D34G+D104A, D34G+D104G, D34G+E108S, D34G+S111A, D34G+S111K, D34G+S111R,D34G+I114Q, D34G+I114M, D34G+I114W, D34G+K116R, D34G+D118K, D34G+T119R,D34G+S131T, D34G+E133R, D34G+E133Q, D34G+D135P, D34G+A136P, D34G+D139A,D34G+D139R, D34G+K142M, D34G+K142V, D34G+K142S, D34G+K142R, D34G+Q143R,D34G+N150T, D34G+N150R, D34G+N150S, D34G+Q169A, D34G+Q169R, D34G+Q169K,D34G+H172R, D34G+Y174R, D34G+Y174L, D34G+Y174W, D34G+Y174F, D34G+R176Q,D34G+E177S, D34G+E177Y, D34G+N180R, D34G+P183T, D34G+P183G, D34G+Q184E,D34G+Q184K, D34G+R185G, D34G+Y196W, D34G+Y196F, D34G+N200T, D34G+S202R,D34G+Q203T, D34G+R205K, D34G+R210L, D34G+R210G, D34G+R210M, D34G+N213V,D34G+N213D, D34G+T228S, D34G+N229D, D34G+E234F, D34G+E234Y, D34G+A235K,D34G+A235R, D34G+S241C, D34G+Q243K, D34G+Q243E, D34G+R244K, D34G+R244V,D34G+A250G, D34G+K254Y, D34G+G257W, D34G+G257E, D34G+G257A, D34G+W260F,D34G+W260Y, D34G+W260L, D34G+W260T, D34G+Y262F, D34G+S266A, D34G+D268N,D34G+A270D, D34G+N272M, D34G+N272T, D34G+N273E, D34G+N273D, D34G+A276E,D34G+A276W, D34G+A276D, D34G+N279D, D34G+N279E, D34G+T280L, D34G+N283W,D34G+N283H, D34G+Y286W, D34G+Y286F, D34G+L288I, D34G+E290A, D34G+L294P,D34G+L294K, D34G+L294I, D34G+L294R, D34G+L294V, D34G+L294H, D34G+S295K,D34G+S295V, D34G+S295P, D34G+S295L, D34G+S295R, D34G+S295A, D34G+S295N,D34G+S295M, D34G+S295I, D34G+T296S, D34G+F298Y, Q35L+T37P, Q35L+E41V,Q35L+E41 N, Q35L+N45G, Q35L+G47S, Q35L+G47A, Q35L+D57N, Q35L+G59Q,Q35L+Q60R, Q35L+K63R, Q35L+K63Q, Q35L+D65E, Q35L+R70K, Q35L+N71S,Q35L+S74K, Q35L+E77T, Q35L+E77N, Q35L+D78G, Q35L+H80K, Q35L+V82R,Q35L+V82I, Q35L+V82S, Q35L+A83P, Q35L+A83S, Q35L+Y93Q, Q35L+Y93A,Q35L+S95D, Q35L+A97R, Q35L+S98P, Q35L+S98D, Q35L+N100Y, Q35L+D104A,Q35L+D104G, Q35L+E108S, Q35L+S111A, Q35L+S111K, Q35L+S111R, Q35L+I114Q,Q35L+I114M, Q35L+I114W, Q35L+K116R, Q35L+D118K, Q35L+T119R, Q35L+S131T,Q35L+E133R, Q35L+E133Q, Q35L+D135P, Q35L+A136P, Q35L+D139A, Q35L+D139R,Q35L+K142M, Q35L+K142V, Q35L+K142S, Q35L+K142R, Q35L+Q143R, Q35L+N150T,Q35L+N150R, Q35L+N150S, Q35L+Q169A, Q35L+Q169R, Q35L+Q169K, Q35L+H172R,Q35L+Y174R, Q35L+Y174L, Q35L+Y174W, Q35L+Y174F, Q35L+R176Q, Q35L+E177S,Q35L+E177Y, Q35L+N180R, Q35L+P183T, Q35L+P183G, Q35L+Q184E, Q35L+Q184K,Q35L+R185G, Q35L+Y196W, Q35L+Y196F, Q35L+N200T, Q35L+S202R, Q35L+Q203T,Q35L+R205K, Q35L+R210L, Q35L+R210G, Q35L+R210M, Q35L+N213V, Q35L+N213D,Q35L+T228S, Q35L+N229D, Q35L+E234F, Q35L+E234Y, Q35L+A235K, Q35L+A235R,Q35L+S241C, Q35L+Q243K, Q35L+Q243E, Q35L+R244K, Q35L+R244V, Q35L+A250G,Q35L+K254Y, Q35L+G257W, Q35L+G257E, Q35L+G257A, Q35L+W260F, Q35L+W260Y,Q35L+W260L, Q35L+W260T, Q35L+Y262F, Q35L+S266A, Q35L+D268N, Q35L+A270D,Q35L+N272M, Q35L+N272T, Q35L+N273E, Q35L+N273D, Q35L+A276E, Q35L+A276W,Q35L+A276D, Q35L+N279D, Q35L+N279E, Q35L+T280L, Q35L+N283W, Q35L+N283H,Q35L+Y286W, Q35L+Y286F, Q35L+L288I, Q35L+E290A, Q35L+L294P, Q35L+L294K,Q35L+L294I, Q35L+L294R, Q35L+L294V, Q35L+L294H, Q35L+S295K, Q35L+S295V,Q35L+S295P, Q35L+S295L, Q35L+S295R, Q35L+S295A, Q35L+S295N, Q35L+S295M,Q35L+S295I, Q35L+T296S, Q35L+F298Y, T37P+E41V, T37P+E41N, T37P+N45G,T37P+G47S, T37P+G47A, T37P+D57N, T37P+G59Q, T37P+Q60R, T37P+K63R,T37P+K63Q, T37P+D65E, T37P+R70K, T37P+N71S, T37P+S74K, T37P+E77T,T37P+E77N, T37P+D78G, T37P+H80K, T37P+V82R, T37P+V82I, T37P+V82S,T37P+A83P, T37P+A83S, T37P+Y93Q, T37P+Y93A, T37P+S95D, T37P+A97R,T37P+S98P, T37P+S98D, T37P+N100Y, T37P+D104A, T37P+D104G, T37P+E108S,T37P+S111A, T37P+S111K, T37P+S111R, T37P+I114Q, T37P+I114M, T37P+I114W,T37P+K116R, T37P+D118K, T37P+T119R, T37P+S131T, T37P+E133R, T37P+E133Q,T37P+D135P, T37P+A136P, T37P+D139A, T37P+D139R, T37P+K142M, T37P+K142V,T37P+K142S, T37P+K142R, T37P+Q143R, T37P+N150T, T37P+N150R, T37P+N150S,T37P+Q169A, T37P+Q169R, T37P+Q169K, T37P+H172R, T37P+Y174R, T37P+Y174L,T37P+Y174W, T37P+Y174F, T37P+R176Q, T37P+E177S, T37P+E177Y, T37P+N180R,T37P+P183T, T37P+P183G, T37P+Q184E, T37P+Q184K, T37P+R185G, T37P+Y196W,T37P+Y196F, T37P+N200T, T37P+S202R, T37P+Q203T, T37P+R205K, T37P+R210L,T37P+R210G, T37P+R210M, T37P+N213V, T37P+N213D, T37P+T228S, T37P+N229D,T37P+E234F, T37P+E234Y, T37P+A235K, T37P+A235R, T37P+S241C, T37P+Q243K,T37P+Q243E, T37P+R244K, T37P+R244V, T37P+A250G, T37P+K254Y, T37P+G257W,T37P+G257E, T37P+G257A, T37P+W260F, T37P+W260Y, T37P+W260L, T37P+W260T,T37P+Y262F, T37P+S266A, T37P+D268N, T37P+A270D, T37P+N272M, T37P+N272T,T37P+N273E, T37P+N273D, T37P+A276E, T37P+A276W, T37P+A276D, T37P+N279D,T37P+N279E, T37P+T280L, T37P+N283W, T37P+N283H, T37P+Y286W, T37P+Y286F,T37P+L288I, T37P+E290A, T37P+L294P, T37P+L294K, T37P+L294I, T37P+L294R,T37P+L294V, T37P+L294H, T37P+S295K, T37P+S295V, T37P+S295P, T37P+S295L,T37P+S295R, T37P+S295A, T37P+S295N, T37P+S295M, T37P+S295I, T37P+T296S,T37P+F298Y, E41V+N45G, E41V+G47S, E41V+G47A, E41V+D57N, E41V+G59Q,E41V+Q60R, E41V+K63R, E41V+K63Q, E41V+D65E, E41V+R70K, E41V+N71S,E41V+S74K, E41V+E77T, E41V+E77N, E41V+D78G, E41V+H80K, E41V+V82R,E41V+V82I, E41V+V82S, E41V+A83P, E41V+A83S, E41V+Y93Q, E41V+Y93A,E41V+S95D, E41V+A97R, E41V+S98P, E41V+S98D, E41V+N100Y, E41V+D104A,E41V+D104G, E41V+E108S, E41V+S111A, E41V+S111K, E41V+S111R, E41V+I114Q,E41V+I114M, E41V+I114W, E41V+K116R, E41V+D118K, E41V+T119R, E41V+S131T,E41V+E133R, E41V+E133Q, E41V+D135P, E41V+A136P, E41V+D139A, E41V+D139R,E41V+K142M, E41V+K142V, E41V+K142S, E41V+K142R, E41V+Q143R, E41V+N150T,E41V+N150R, E41V+N150S, E41V+Q169A, E41V+Q169R, E41V+Q169K, E41V+H172R,E41V+Y174R, E41V+Y174L, E41V+Y174W, E41V+Y174F, E41V+R176Q, E41V+E177S,E41V+E177Y, E41V+N180R, E41V+P183T, E41V+P183G, E41V+Q184E, E41V+Q184K,E41V+R185G, E41V+Y196W, E41V+Y196F, E41V+N200T, E41V+S202R, E41V+Q203T,E41V+R205K, E41V+R210L, E41V+R210G, E41V+R210M, E41V+N213V, E41V+N213D,E41V+T228S, E41V+N229D, E41V+E234F, E41V+E234Y, E41V+A235K, E41V+A235R,E41V+S241C, E41V+Q243K, E41V+Q243E, E41V+R244K, E41V+R244V, E41V+A250G,E41V+K254Y, E41V+G257W, E41V+G257E, E41V+G257A, E41V+W260F, E41V+W260Y,E41V+W260L, E41V+W260T, E41V+Y262F, E41V+S266A, E41V+D268N, E41V+A270D,E41V+N272M, E41V+N272T, E41V+N273E, E41V+N273D, E41V+A276E, E41V+A276W,E41V+A276D, E41V+N279D, E41V+N279E, E41V+T280L, E41V+N283W, E41V+N283H,E41V+Y286W, E41V+Y286F, E41V+L288I, E41V+E290A, E41V+L294P, E41V+L294K,E41V+L294I, E41V+L294R, E41V+L294V, E41V+L294H, E41V+S295K, E41V+S295V,E41V+S295P, E41V+S295L, E41V+S295R, E41V+S295A, E41V+S295N, E41V+S295M,E41V+S295I, E41V+T296S, E41V+F298Y, E41N+N45G, E41N+G47S, E41N+G47A,E41N+D57N, E41N+G59Q, E41N+Q60R, E41N+K63R, E41N+K63Q, E41N+D65E,E41N+R70K, E41N+N71S, E41N+S74K, E41N+E77T, E41N+E77N, E41N+D78G,E41N+H80K, E41N+V82R, E41N+V82I, E41N+V82S, E41N+A83P, E41N+A83S,E41N+Y93Q, E41N+Y93A, E41N+S95D, E41N+A97R, E41N+S98P, E41N+S98D,E41N+N100Y, E41N+D104A, E41N+D104G, E41N+E108S, E41N+S111A, E41N+S111K,E41N+S111R, E41N+I114Q, E41N+I114M, E41N+I114W, E41N+K116R, E41N+D118K,E41N+T119R, E41N+S131T, E41N+E133R, E41N+E133Q, E41N+D135P, E41N+A136P,E41N+D139A, E41N+D139R, E41N+K142M, E41N+K142V, E41N+K142S, E41N+K142R,E41N+Q143R, E41N+N150T, E41N+N150R, E41N+N150S, E41N+Q169A, E41N+Q169R,E41N+Q169K, E41N+H172R, E41N+Y174R, E41N+Y174L, E41N+Y174W, E41N+Y174F,E41N+R176Q, E41N+E177S, E41N+E177Y, E41N+N180R, E41N+P183T, E41N+P183G,E41N+Q184E, E41N+Q184K, E41N+R185G, E41N+Y196W, E41N+Y196F, E41N+N200T,E41N+S202R, E41N+Q203T, E41N+R205K, E41N+R210L, E41N+R210G, E41N+R210M,E41N+N213V, E41N+N213D, E41N+T228S, E41N+N229D, E41N+E234F, E41N+E234Y,E41N+A235K, E41N+A235R, E41N+S241C, E41N+Q243K, E41N+Q243E, E41N+R244K,E41N+R244V, E41N+A250G, E41N+K254Y, E41N+G257W, E41N+G257E, E41N+G257A,E41N+W260F, E41N+W260Y, E41N+W260L, E41N+W260T, E41N+Y262F, E41N+S266A,E41N+D268N, E41N+A270D, E41N+N272M, E41N+N272T, E41N+N273E, E41N+N273D,E41N+A276E, E41N+A276W, E41N+A276D, E41N+N279D, E41N+N279E, E41N+T280L,E41N+N283W, E41N+N283H, E41N+Y286W, E41N+Y286F, E41N+L288I, E41N+E290A,E41N+L294P, E41N+L294K, E41N+L294I, E41N+L294R, E41N+L294V, E41N+L294H,E41N+S295K, E41N+S295V, E41N+S295P, E41N+S295L, E41N+S295R, E41N+S295A,E41N+S295N, E41N+S295M, E41N+S295I, E41N+T296S, E41N+F298Y, N45G+G47S,N45G+G47A, N45G+D57N, N45G+G59Q, N45G+Q60R, N45G+K63R, N45G+K63Q,N45G+D65E, N45G+R70K, N45G+N71S, N45G+S74K, N45G+E77T, N45G+E77N,N45G+D78G, N45G+H80K, N45G+V82R, N45G+V82I, N45G+V82S, N45G+A83P,N45G+A83S, N45G+Y93Q, N45G+Y93A, N45G+S95D, N45G+A97R, N45G+S98P,N45G+S98D, N45G+N100Y, N45G+D104A, N45G+D104G, N45G+E108S, N45G+S111A,N45G+S111K, N45G+S111R, N45G+I114Q, N45G+I114M, N45G+I114W, N45G+K116R,N45G+D118K, N45G+T119R, N45G+S131T, N45G+E133R, N45G+E133Q, N45G+D135P,N45G+A136P, N45G+D139A, N45G+D139R, N45G+K142M, N45G+K142V, N45G+K142S,N45G+K142R, N45G+Q143R, N45G+N150T, N45G+N150R, N45G+N150S, N45G+Q169A,N45G+Q169R, N45G+Q169K, N45G+H172R, N45G+Y174R, N45G+Y174L, N45G+Y174W,N45G+Y174F, N45G+R176Q, N45G+E177S, N45G+E177Y, N45G+N180R, N45G+P183T,N45G+P183G, N45G+Q184E, N45G+Q184K, N45G+R185G, N45G+Y196W, N45G+Y196F,N45G+N200T, N45G+S202R, N45G+Q203T, N45G+R205K, N45G+R210L, N45G+R210G,N45G+R210M, N45G+N213V, N45G+N213D, N45G+T228S, N45G+N229D, N45G+E234F,N45G+E234Y, N45G+A235K, N45G+A235R, N45G+S241C, N45G+Q243K, N45G+Q243E,N45G+R244K, N45G+R244V, N45G+A250G, N45G+K254Y, N45G+G257W, N45G+G257E,N45G+G257A, N45G+W260F, N45G+W260Y, N45G+W260L, N45G+W260T, N45G+Y262F,N45G+S266A, N45G+D268N, N45G+A270D, N45G+N272M, N45G+N272T, N45G+N273E,N45G+N273D, N45G+A276E, N45G+A276W, N45G+A276D, N45G+N279D, N45G+N279E,N45G+T280L, N45G+N283W, N45G+N283H, N45G+Y286W, N45G+Y286F, N45G+L288I,N45G+E290A, N45G+L294P, N45G+L294K, N45G+L294I, N45G+L294R, N45G+L294V,N45G+L294H, N45G+S295K, N45G+S295V, N45G+S295P, N45G+S295L, N45G+S295R,N45G+S295A, N45G+S295N, N45G+S295M, N45G+S295I, N45G+T296S, N45G+F298Y,G47S+D57N, G47S+G59Q, G47S+Q60R, G47S+K63R, G47S+K63Q, G47S+D65E,G47S+R70K, G47S+N71S, G47S+S74K, G47S+E77T, G47S+E77N, G47S+D78G,G47S+H80K, G47S+V82R, G47S+V82I, G47S+V82S, G47S+A83P, G47S+A83S,G47S+Y93Q, G47S+Y93A, G47S+S95D, G47S+A97R, G47S+S98P, G47S+S98D,G47S+N100Y, G47S+D104A, G47S+D104G, G47S+E108S, G47S+S111A, G47S+S111 K,G47S+S111R, G47S+I114Q, G47S+I114M, G47S+I114W, G47S+K116R, G47S+D118K,G47S+T119R, G47S+S131T, G47S+E133R, G47S+E133Q, G47S+D135P, G47S+A136P,G47S+D139A, G47S+D139R, G47S+K142M, G47S+K142V, G47S+K142S, G47S+K142R,G47S+Q143R, G47S+N150T, G47S+N150R, G47S+N150S, G47S+Q169A, G47S+Q169R,G47S+Q169K, G47S+H172R, G47S+Y174R, G47S+Y174L, G47S+Y174W, G47S+Y174F,G47S+R176Q, G47S+E177S, G47S+E177Y, G47S+N180R, G47S+P183T, G47S+P183G,G47S+Q184E, G47S+Q184K, G47S+R185G, G47S+Y196W, G47S+Y196F, G47S+N200T,G47S+S202R, G47S+Q203T, G47S+R205K, G47S+R210L, G47S+R210G, G47S+R210M,G47S+N213V, G47S+N213D, G47S+T228S, G47S+N229D, G47S+E234F, G47S+E234Y,G47S+A235K, G47S+A235R, G47S+S241C, G47S+Q243K, G47S+Q243E, G47S+R244K,G47S+R244V, G47S+A250G, G47S+K254Y, G47S+G257W, G47S+G257E, G47S+G257A,G47S+W260F, G47S+W260Y, G47S+W260L, G47S+W260T, G47S+Y262F, G47S+S266A,G47S+D268N, G47S+A270D, G47S+N272M, G47S+N272T, G47S+N273E, G47S+N273D,G47S+A276E, G47S+A276W, G47S+A276D, G47S+N279D, G47S+N279E, G47S+T280L,G47S+N283W, G47S+N283H, G47S+Y286W, G47S+Y286F, G47S+L288I, G47S+E290A,G47S+L294P, G47S+L294K, G47S+L294I, G47S+L294R, G47S+L294V, G47S+L294H,G47S+S295K, G47S+S295V, G47S+S295P, G47S+S295L, G47S+S295R, G47S+S295A,G47S+S295N, G47S+S295M, G47S+S295I, G47S+T296S, G47S+F298Y, G47A+D57N,G47A+G59Q, G47A+Q60R, G47A+K63R, G47A+K63Q, G47A+D65E, G47A+R70K,G47A+N71S, G47A+S74K, G47A+E77T, G47A+E77N, G47A+D78G, G47A+H80K,G47A+V82R, G47A+V82I, G47A+V82S, G47A+A83P, G47A+A83S, G47A+Y93Q,G47A+Y93A, G47A+S95D, G47A+A97R, G47A+S98P, G47A+S98D, G47A+N100Y,G47A+D104A, G47A+D104G, G47A+E108S, G47A+S111A, G47A+S111K, G47A+S111R,G47A+I114Q, G47A+I114M, G47A+I114W, G47A+K116R, G47A+D118K, G47A+T119R,G47A+S131T, G47A+E133R, G47A+E133Q, G47A+D135P, G47A+A136P, G47A+D139A,G47A+D139R, G47A+K142M, G47A+K142V, G47A+K142S, G47A+K142R, G47A+Q143R,G47A+N150T, G47A+N150R, G47A+N 150S, G47A+Q169A, G47A+Q169R, G47A+Q169K,G47A+H172R, G47A+Y174R, G47A+Y174L, G47A+Y174W, G47A+Y174F, G47A+R176Q,G47A+E177S, G47A+E177Y, G47A+N180R, G47A+P183T, G47A+P183G, G47A+Q184E,G47A+Q184K, G47A+R185G, G47A+Y196W, G47A+Y196F, G47A+N200T, G47A+S202R,G47A+Q203T, G47A+R205K, G47A+R210L, G47A+R210G, G47A+R210M, G47A+N213V,G47A+N213D, G47A+T228S, G47A+N229D, G47A+E234F, G47A+E234Y, G47A+A235K,G47A+A235R, G47A+S241C, G47A+Q243K, G47A+Q243E, G47A+R244 K, G47A+R244V,G47A+A250G, G47A+K254Y, G47A+G257W, G47A+G257E, G47A+G257A, G47A+W260F,G47A+W260Y, G47A+W260L, G47A+W260T, G47A+Y262F, G47A+S266A, G47A+D268N,G47A+A270D, G47A+N272M, G47A+N272T, G47A+N273E, G47A+N273D, G47A+A276E,G47A+A276W, G47A+A276D, G47A+N279D, G47A+N279E, G47A+T280L, G47A+N283W,G47A+N283H, G47A+Y286W, G47A+Y286F, G47A+L288I, G47A+E290A, G47A+L294P,G47A+L294K, G47A+L294I, G47A+L294R, G47A+L294V, G47A+L294H, G47A+S295K,G47A+S295V, G47A+S295P, G47A+S295L, G47A+S295R, G47A+S295A, G47A+S295N,G47A+S295M, G47A+S295I, G47A+T296S, G47A+F298Y, D57N+G59Q, D57N+Q60R,D57N+K63R, D57N+K63Q, D57N+D65E, D57N+R70K, D57N+N71S, D57N+S74K,D57N+E77T, D57N+E77N, D57N+D78G, D57N+H80K, D57N+V82R, D57N+V82I,D57N+V82S, D57N+A83P, D57N+A83S, D57N+Y93Q, D57N+Y93A, D57N+S95D,D57N+A97R, D57N+S98P, D57N+S98D, D57N+N100Y, D57N+D104A, D57N+D104G,D57N+E108S, D57N+S111A, D57N+S111 K, D57N+S111R, D57N+I114Q, D57N+I114M,D57N+I114W, D57N+K116R, D57N+D118K, D57N+T119R, D57N+S131T, D57N+E133R,D57N+E133Q, D57N+D135P, D57N+A136P, D57N+D139A, D57N+D139R, D57N+K142M,D57N+K142V, D57N+K142S, D57N+K142R, D57N+Q143R, D57N+N150T, D57N+N150R,D57N+N150S, D57N+Q169A, D57N+Q169R, D57N+Q169K, D57N+H172R, D57N+Y174R,D57N+Y174L, D57N+Y174W, D57N+Y174F, D57N+R176Q, D57N+E177S, D57N+E177Y,D57N+N180R, D57N+P183T, D57N+P183G, D57N+Q184E, D57N+Q184K, D57N+R185G,D57N+Y196W, D57N+Y196F, D57N+N200T, D57N+S202R, D57N+Q203T, D57N+R205K,D57N+R210L, D57N+R210G, D57N+R210M, D57N+N213V, D57N+N213D, D57N+T228S,D57N+N229D, D57N+E234F, D57N+E234Y, D57N+A235K, D57N+A235R, D57N+S241C,D57N+Q243K, D57N+Q243E, D57N+R244K, D57N+R244V, D57N+A250G, D57N+K254Y,D57N+G257W, D57N+G257E, D57N+G257A, D57N+W260F, D57E+W260Y, D57E+W260L,D57E+W260T, D57N+Y262F, D57N+S266A, D57N+D268N, D57N+A270D, D57N+N272M,D57N+N272T, D57N+N273E, D57N+N273D, D57N+A276E, D57N+A276W, D57N+A276D,D57N+N279D, D57N+N279E, D57N+T280L, D57N+N283W, D57N+N283H, D57N+Y286W,D57N+Y286F, D57N+L288I, D57N+E290A, D57N+L294P, D57N+L294K, D57N+L294I,D57N+L294R, D57N+L294V, D57N+L294H, D57N+S295K, D57N+S295V, D57N+S295P,D57N+S295L, D57N+S295R, D57N+S295A, D57N+S295N, D57N+S295M, D57N+S295I,D57N+T296S, D57N+F298Y, G59Q+Q60R, G59Q+K63R, G59Q+K63Q, G59Q+D65E,G59Q+R70K, G59Q+N71S, G59Q+S74K, G59Q+E77T, G59Q+E77N, G59Q+D78G,G59Q+H80K, G59Q+V82R, G59Q+V82I, G59Q+V82S, G59Q+A83P, G59Q+A83S,G59Q+Y93Q, G59Q+Y93A, G59Q+S95D, G59Q+A97R, G59Q+S98P, G59Q+S98D,G59Q+N100Y, G59Q+D104A, G59Q+D104G, G59Q+E108S, G59Q+S111A, G59Q+S111K,G59Q+S111R, G59Q+I114Q, G59Q+I114M, G59Q+I114W, G59Q+K116R, G59Q+D118K,G59Q+T119R, G59Q+S131T, G59Q+E133R, G59Q+E133Q, G59Q+D135P, G59Q+A136P,G59Q+D139A, G59Q+D139R, G59Q+K142M, G59Q+K142V, G59Q+K142S, G59Q+K142R,G59Q+Q143R, G59Q+N150T, G59Q+N150R, G59Q+N150S, G59Q+Q169A, G59Q+Q169R,G59Q+Q169K, G59Q+H172R, G59Q+Y174R, G59Q+Y174L, G59Q+Y174W, G59Q+Y174F,G59Q+R176Q, G59Q+E177S, G59Q+E177Y, G59Q+N180R, G59Q+P183T, G59Q+P183G,G59Q+Q184E, G59Q+Q184K, G59Q+R185G, G59Q+Y196W, G59Q+Y196F, G59Q+N200T,G59Q+S202R, G59Q+Q203T, G59Q+R205K, G59Q+R210L, G59Q+R210G, G59Q+R210M,G59Q+N213V, G59Q+N213D, G59Q+T228S, G59Q+N229D, G59Q+E234F, G59Q+E234Y,G59Q+A235K, G59Q+A235R, G59Q+S241C, G59Q+Q243K, G59Q+Q243E, G59Q+R244K,G59Q+R244V, G59Q+A250G, G59Q+K254Y, G59Q+G257W, G59Q+G257E, G59Q+G257A,G59Q+W260F, G59Q+W260Y, G59Q+W260L, G59Q+W260T, G59Q+Y262F, G59Q+S266A,G59Q+D268N, G59Q+A270D, G59Q+N272M, G59Q+N272T, G59Q+N273E, G59Q+N273D,G59Q+A276E, G59Q+A276W, G59Q+A276D, G59Q+N279D, G59Q+N279E, G59Q+T280L,G59Q+N283W, G59Q+N283H, G59Q+Y286W, G59Q+Y286F, G59Q+L288I, G59Q+E290A,G59Q+L294P, G59Q+L294K, G59Q+L294I, G59Q+L294R, G59Q+L294V, G59Q+L294H,G59Q+S295K, G59Q+S295V, G59Q+S295P, G59Q+S295L, G59Q+S295R, G59Q+S295A,G59Q+S295N, G59Q+S295M, G59Q+S295I, G59Q+T296S, G59Q+F298Y, Q60R+K63R,Q60R+K63Q, Q60R+D65E, Q60R+R70K, Q60R+N71S, Q60R+S74K, Q60R+E77T,Q60R+E77N, Q60R+D78G, Q60R+H80K, Q60R+V82R, Q60R+V82I, Q60R+V82S,Q60R+A83P, Q60R+A83S, Q60R+Y93Q, Q60R+Y93A, Q60R+S95D, Q60R+A97R,Q60R+S98P, Q60R+S98D, Q60R+N100Y, Q60R+D104A, Q60R+D104G, Q60R+E108S,Q60R+S111A, Q60R+S111 K, Q60R+S111R, Q60R+I114Q, Q60R+I114M, Q60R+I114W,Q60R+K116R, Q60R+D118K, Q60R+T119R, Q60R+S131T, Q60R+E133R, Q60R+E133Q,Q60R+D135P, Q60R+A136P, Q60R+D139A, Q60R+D139R, Q60R+K142M, Q60R+K142V,Q60R+K142S, Q60R+K142R, Q60R+Q143R, Q60R+N150T, Q60R+N150R, Q60R+N150S,Q60R+Q169A, Q60R+Q169R, Q60R+Q169K, Q60R+H172R, Q60R+Y174R, Q60R+Y174L,Q60R+Y174W, Q60R+Y174F, Q60R+R176Q, Q60R+E177S, Q60R+E177Y, Q60R+N180R,Q60R+P183T, Q60R+P183G, Q60R+Q184E, Q60R+Q184K, Q60R+R185G, Q60R+Y196W,Q60R+Y196F, Q60R+N200T, Q60R+S202R, Q60R+Q203T, Q60R+R205K, Q60R+R210L,Q60R+R210G, Q60R+R210M, Q60R+N213V, Q60R+N213D, Q60R+T228S, Q60R+N229D,Q60R+E234F, Q60R+E234Y, Q60R+A235K, Q60R+A235R, Q60R+S241C, Q60R+Q243K,Q60R+Q243E, Q60R+R244K, Q60R+R244V, Q60R+A250G, Q60R+K254Y, Q60R+G257W,Q60R+G257E, Q60R+G257A, Q60R+W260F, Q60R+W260Y, Q60R+W260L, Q60R+W260T,Q60R+Y262F, Q60R+S266A, Q60R+D268N, Q60R+A270D, Q60R+N272M, Q60R+N272T,Q60R+N273E, Q60R+N273D, Q60R+A276E, Q60R+A276W, Q60R+A276D, Q60R+N279D,Q60R+N279E, Q60R+T280L, Q60R+N283W, Q60R+N283H, Q60R+Y286W, Q60R+Y286F,Q60R+L288I, Q60R+E290A, Q60R+L294P, Q60R+L294K, Q60R+L294I, Q60R+L294R,Q60R+L294V, Q60R+L294H, Q60R+S295K, Q60R+S295V, Q60R+S295P, Q60R+S295L,Q60R+S295R, Q60R+S295A, Q60R+S295N, Q60R+S295M, Q60R+S295I, Q60R+T296S,Q60R+F298Y, K63R+D65E, K63R+R70K, K63R+N71S, K63R+S74K, K63R+E77T,K63R+E77N, K63R+D78G, K63R+H80K, K63R+V82R, K63R+V82I, K63R+V82S,K63R+A83P, K63R+A83S, K63R+Y93Q, K63R+Y93A, K63R+S95D, K63R+A97R,K63R+S98P, K63R+S98D, K63R+N100Y, K63R+D104A, K63R+D104G, K63R+E108S,K63R+S111A, K63R+S111K, K63R+S111R, K63R+I114Q, K63R+I114M, K63R+I114W,K63R+K116R, K63R+D118K, K63R+T119R, K63R+S131T, K63R+E133R, K63R+E133Q,K63R+D135P, K63R+A136P, K63R+D139A, K63R+D139R, K63R+K142M, K63R+K142V,K63R+K142S, K63R+K142R, K63R+Q143R, K63R+N150T, K63R+N150R, K63R+N150S,K63R+Q169A, K63R+Q169R, K63R+Q169K, K63R+H172R, K63R+Y174R, K63R+Y174L,K63R+Y174W, K63R+Y174F, K63R+R176Q, K63R+E177S, K63R+E177Y, K63R+N180R,K63R+P183T, K63R+P183G, K63R+Q184E, K63R+Q184K, K63R+R185G, K63R+Y196W,K63R+Y196F, K63R+N200T, K63R+S202R, K63R+Q203T, K63R+R205K, K63R+R210L,K63R+R210G, K63R+R210M, K63R+N213V, K63R+N213D, K63R+T228S, K63R+N229D,K63R+E234F, K63R+E234Y, K63R+A235K, K63R+A235R, K63R+S241C, K63R+Q243K,K63R+Q243E, K63R+R244K, K63R+R244V, K63R+A250G, K63R+K254Y, K63R+G257W,K63R+G257E, K63R+G257A, K63R+W260F, K63R+W260Y, K63R+W260L, K63R+W260T,K63R+Y262F, K63R+S266A, K63R+D268N, K63R+A270D, K63R+N272M, K63R+N272T,K63R+N273E, K63R+N273D, K63R+A276E, K63R+A276W, K63R+A276D, K63R+N279D,K63R+N279E, K63R+T280L, K63R+N283W, K63R+N283H, K63R+Y286W, K63R+Y286F,K63R+L288I, K63R+E290A, K63R+L294P, K63R+L294K, K63R+L294I, K63R+L294R,K63R+L294V, K63R+L294H, K63R+S295K, K63R+S295V, K63R+S295P, K63R+S295L,K63R+S295R, K63R+S295A, K63R+S295N, K63R+S295M, K63R+S295I, K63R+T296S,K63R+F298Y, K63Q+D65E, K63Q+R70K, K63Q+N71S, K63Q+S74K, K63Q+E77T,K63Q+E77N, K63Q+D78G, K63Q+H80K, K63Q+V82R, K63Q+V82 I, K63Q+V82S,K63Q+A83P, K63Q+A83S, K63Q+Y93Q, K63Q+Y93A, K63Q+S95D, K63Q+A97R,K63Q+S98P, K63Q+S98D, K63Q+N100Y, K63Q+D104A, K63Q+D104G, K63Q+E108S,K63Q+S111A, K63Q+S111K, K63Q+S111R, K63Q+I114Q, K63Q+I114M, K63Q+I114W,K63Q+K116R, K63Q+D118K, K63Q+T119R, K63Q+S131T, K63Q+E133R, K63Q+E133Q,K63Q+D135P, K63Q+A136P, K63Q+D139A, K63Q+D139R, K63Q+K142M, K63Q+K142V,K63Q+K142S, K63Q+K142R, K63Q+Q143R, K63Q+N150T, K63Q+N150R, K63Q+N150S,K63Q+Q169A, K63Q+Q169R, K63Q+Q169K, K63Q+H172R, K63Q+Y174R, K63Q+Y174L,K63Q+Y174W, K63Q+Y174F, K63Q+R176Q, K63Q+E177S, K63Q+E177Y, K63Q+N180R,K63Q+P183T, K63Q+P183G, K63Q+Q184E, K63Q+Q184K, K63Q+R185G, K63Q+Y196W,K63Q+Y196F, K63Q+N200T, K63Q+S202R, K63Q+Q203T, K63Q+R205K, K63Q+R210L,K63Q+R210G, K63Q+R210M, K63Q+N213V, K63Q+N213D, K63Q+T228S, K63Q+N229D,K63Q+E234F, K63Q+E234Y, K63Q+A235K, K63Q+A235R, K63Q+S241C, K63Q+Q243K,K63Q+Q243E, K63Q+R244K, K63Q+R244V, K63Q+A250G, K63Q+K254Y, K63Q+G257W,K63Q+G257E, K63Q+G257A, K63Q+W260F, K63Q+W260Y, K63Q+W260L, K63Q+W260T,K63Q+Y262F, K63Q+S266A, K63Q+D268N, K63Q+A270D, K63Q+N272M, K63Q+N272T,K63Q+N273E, K63Q+N273D, K63Q+A276E, K63Q+A276W, K63Q+A276D, K63Q+N279D,K63Q+N279E, K63Q+T280L, K63Q+N283W, K63Q+N283H, K63Q+Y286W, K63Q+Y286F,K63Q+L288I, K63Q+E290A, K63Q+L294P, K63Q+L294K, K63Q+L294I, K63Q+L294R,K63Q+L294V, K63Q+L294H, K63Q+S295K, K63Q+S295V, K63Q+S295P, K63Q+S295L,K63Q+S295R, K63Q+S295A, K63Q+S295N, K63Q+S295M, K63Q+S295I, K63Q+T296S,K63Q+F298Y, D65E+R70K, D65E+N71S, D65E+S74K, D65E+E77T, D65E+E77N,D65E+D78G, D65E+H80K, D65E+V82R, D65E+V82I, D65E+V82S, D65E+A83P,D65E+A83S, D65E+Y93Q, D65E+Y93A, D65E+S95D, D65E+A97R, D65E+S98P,D65E+S98D, D65E+N100Y, D65E+D104A, D65E+D104G, D65E+E108S, D65E+S111A,D65E+S111 K, D65E+S111R, D65E+I114Q, D65E+I114M, D65E+I114W, D65E+K116R,D65E+D118K, D65E+T119R, D65E+S131T, D65E+E133R, D65E+E133Q, D65E+D135P,D65E+A136P, D65E+D139A, D65E+D139R, D65E+K142M, D65E+K142V, D65E+K142S,D65E+K142R, D65E+Q143R, D65E+N150T, D65E+N150R, D65E+N150S, D65E+Q169A,D65E+Q169R, D65E+Q169K, D65E+H172R, D65E+Y174R, D65E+Y174L, D65E+Y174W,D65E+Y174F, D65E+R176Q, D65E+E177S, D65E+E177Y, D65E+N180R, D65E+P183T,D65E+P183G, D65E+Q184E, D65E+Q184K, D65E+R185G, D65E+Y196W, D65E+Y196F,D65E+N200T, D65E+S202R, D65E+Q203T, D65E+R205K, D65E+R210L, D65E+R210G,D65E+R210M, D65E+N213V, D65E+N213D, D65E+T228S, D65E+N229D, D65E+E234F,D65E+E234Y, D65E+A235K, D65E+A235R, D65E+S241C, D65E+Q243K, D65E+Q243E,D65E+R244K, D65E+R244V, D65E+A250G, D65E+K254Y, D65E+G257W, D65E+G257E,D65E+G257A, D65E+W260F, D65E+W260Y, D65E+W260L, D65E+W260T, D65E+Y262F,D65E+S266A, D65E+D268N, D65E+A270D, D65E+N272M, D65E+N272T, D65E+N273E,D65E+N273D, D65E+A276E, D65E+A276W, D65E+A276D, D65E+N279D, D65E+N279E,D65E+T280L, D65E+N283W, D65E+N283H, D65E+Y286W, D65E+Y286F, D65E+L288I,D65E+E290A, D65E+L294P, D65E+L294K, D65E+L294I, D65E+L294R, D65E+L294V,D65E+L294H, D65E+S295K, D65E+S295V, D65E+S295P, D65E+S295L, D65E+S295R,D65E+S295A, D65E+S295N, D65E+S295M, D65E+S295I, D65E+T296S, D65E+F298Y,R70K+N71S, R70K+S74K, R70K+E77T, R70K+E77N, R70K+D78G, R70K+H80K,R70K+V82R, R70K+V82I, R70K+V82S, R70K+A83P, R70K+A83S, R70K+Y93Q,R70K+Y93A, R70K+S95D, R70K+A97R, R70K+S98P, R70K+S98D, R70K+N100Y,R70K+D104A, R70K+D104G, R70K+E108S, R70K+S111A, R70K+S111K, R70K+S111R,R70K+I114Q, R70K+I114M, R70K+I114W, R70K+K116R, R70K+D118K, R70K+T119R,R70K+S131T, R70K+E133R, R70K+E133Q, R70K+D135P, R70K+A136P, R70K+D139A,R70K+D139R, R70K+K142M, R70K+K142V, R70K+K142S, R70K+K142R, R70K+Q143R,R70K+N150T, R70K+N150R, R70K+N150S, R70K+Q169A, R70K+Q169R, R70K+Q169K,R70K+H172R, R70K+Y174R, R70K+Y174L, R70K+Y174W, R70K+Y174F, R70K+R176Q,R70K+E177S, R70K+E177Y, R70K+N180R, R70K+P183T, R70K+P183G, R70K+Q184E,R70K+Q184K, R70K+R185G, R70K+Y196W, R70K+Y196F, R70K+N200T, R70K+S202R,R70K+Q203T, R70K+R205K, R70K+R210L, R70K+R210G, R70K+R210M, R70K+N213V,R70K+N213D, R70K+T228S, R70K+N229D, R70K+E234F, R70K+E234Y, R70K+A235K,R70K+A235R, R70K+S241C, R70K+Q243K, R70K+Q243E, R70K+R244K, R70K+R244V,R70K+A250G, R70K+K254Y, R70K+G257W, R70K+G257E, R70K+G257A, R70K+W260F,R70K+W260Y, R70K+W260L, R70K+W260T, R70K+Y262F, R70K+S266A, R70K+D268N,R70K+A270D, R70K+N272M, R70K+N272T, R70K+N273E, R70K+N273D, R70K+A276E,R70K+A276W, R70K+A276D, R70K+N279D, R70K+N279E, R70K+T280L, R70K+N283W,R70K+N283H, R70K+Y286W, R70K+Y286F, R70K+L288I, R70K+E290A, R70K+L294P,R70K+L294K, R70K+L294I, R70K+L294R, R70K+L294V, R70K+L294H, R70K+S295K,R70K+S295V, R70K+S295P, R70K+S295L, R70K+S295R, R70K+S295A, R70K+S295N,R70K+S295M, R70K+S295I, R70K+T296S, R70K+F298Y, N71S+S74K, N71S+E77T,N71S+E77N, N71S+D78G, N71S+H80K, N71S+V82R, N71S+V82I, N71S+V82S,N71S+A83P, N71S+A83S, N71S+Y93Q, N71S+Y93A, N71S+S95D, N71S+A97R,N71S+S98P, N71S+S98D, N71S+N100Y, N71S+D104A, N71S+D104G, N71S+E108S,N71S+S111A, N71S+S111K, N71S+S111R, N71S+I114Q, N71S+I114M, N71S+I114W,N71S+K116R, N71S+D118K, N71S+T119R, N71S+S131T, N71S+E133R, N71S+E133Q,N71S+D135P, N71S+A136P, N71S+D139A, N71S+D139R, N71S+K142M, N71S+K142V,N71S+K142S, N71S+K142R, N71S+Q143R, N71S+N150T, N71S+N150R, N71S+N150S,N71S+Q169A, N71S+Q169R, N71S+Q169K, N71S+H172R, N71S+Y174R, N71S+Y174L,N71S+Y174W, N71S+Y174F, N71S+R176Q, N71S+E177S, N71S+E177Y, N71S+N180R,N71S+P183T, N71S+P183G, N71S+Q184E, N71S+Q184K, N71S+R185G, N71S+Y196W,N71S+Y196F, N71S+N200T, N71S+S202R, N71S+Q203T, N71S+R205K, N71S+R210L,N71S+R210G, N71S+R210M, N71S+N213V, N71S+N213D, N71S+T228S, N71S+N229D,N71S+E234F, N71S+E234Y, N71S+A235K, N71S+A235R, N71S+S241C, N71S+Q243K,N71S+Q243E, N71S+R244K, N71S+R244V, N71S+A250G, N71S+K254Y, N71S+G257W,N71S+G257E, N71S+G257A, N71S+W260F, N71S+W260Y, N71S+W260L, N71S+W260T,N71S+Y262F, N71S+S266A, N71S+D268N, N71S+A270D, N71S+N272M, N71S+N272T,N71S+N273E, N71S+N273D, N71S+A276E, N71S+A276W, N71S+A276D, N71S+N279D,N71S+N279E, N71S+T280L, N71S+N283W, N71S+N283H, N71S+Y286W, N71S+Y286F,N71S+L288I, N71S+E290A, N71S+L294P, N71S+L294K, N71S+L294I, N71S+L294R,N71S+L294V, N71S+L294H, N71S+S295K, N71S+S295V, N71S+S295P, N71S+S295L,N71S+S295R, N71S+S295A, N71S+S295N, N71S+S295M, N71S+S295I, N71S+T296S,N71S+F298Y, S74K+E77T, S74K+E77N, S74K+D78G, S74K+H80K, S74K+V82R,S74K+V82I, S74K+V82S, S74K+A83P, S74K+A83S, S74K+Y93Q, S74K+Y93A,S74K+S95D, S74K+A97R, S74K+S98P, S74K+S98D, S74K+N100Y, S74K+D104A,S74K+D104G, S74K+E108S, S74K+S111A, S74K+S111K, S74K+S111R, S74K+I114Q,S74K+I114M, S74K+I114W, S74K+K116R, S74K+D118K, S74K+T119R, S74K+S131T,S74K+E133R, S74K+E133Q, S74K+D135P, S74K+A136P, S74K+D139A, S74K+D139R,S74K+K142M, S74K+K142V, S74K+K142S, S74K+K142R, S74K+Q143R, S74K+N150T,S74K+N150R, S74K+N150S, S74K+Q169A, S74K+Q169R, S74K+Q169K, S74K+H172R,S74K+Y174R, S74K+Y174L, S74K+Y174W, S74K+Y174F, S74K+R176Q, S74K+E177S,S74K+E177Y, S74K+N180R, S74K+P183T, S74K+P183G, S74K+Q184E, S74K+Q184K,S74K+R185G, S74K+Y196W, S74K+Y196F, S74K+N200T, S74K+S202R, S74K+Q203T,S74K+R205K, S74K+R210L, S74K+R210G, S74K+R210M, S74K+N213V, S74K+N213D,S74K+T228S, S74K+N229D, S74K+E234F, S74K+E234Y, S74K+A235K, S74K+A235R,S74K+S241C, S74K+Q243K, S74K+Q243E, S74K+R244K, S74K+R244V, S74K+A250G,S74K+K254Y, S74K+G257W, S74K+G257E, S74K+G257A, S74K+W260F, S74K+W260Y,S74K+W260L, S74K+W260T, S74K+Y262F, S74K+S266A, S74K+D268N, S74K+A270D,S74K+N272M, S74K+N272T, S74K+N273E, S74K+N273D, S74K+A276E, S74K+A276W,S74K+A276D, S74K+N279D, S74K+N279E, S74K+T280L, S74K+N283W, S74K+N283H,S74K+Y286W, S74K+Y286F, S74K+L288I, S74K+E290A, S74K+L294P, S74 K+L294K, S74K+L294I, S74K+L294R, S74 K+L294V, S74K+L294H, S74K+S295K,S74K+S295V, S74K+S295P, S74K+S295L, S74K+S295R, S74K+S295A, S74K+S295N,S74 K+S295M, S74 K+S295I, S74 K+T296S, S74 K+F298Y, E77T+D78G,E77T+H80K, E77T+V82R, E77T+V82 I, E77T+V82S, E77T+A83P, E77T+A83S,E77T+Y93Q, E77T+Y93A, E77T+S95D, E77T+A97R, E77T+S98P, E77T+S98D,E77T+N100Y, E77T+D104A, E77T+D104G, E77T+E108S, E77T+S111A, E77T+S111K,E77T+S111R, E77T+I114Q, E77T+I114M, E77T+I114W, E77T+K116R, E77T+D118K,E77T+T119R, E77T+S131T, E77T+E133R, E77T+E133Q, E77T+D135P, E77T+A136P,E77T+D139A, E77T+D139R, E77T+K142M, E77T+K142V, E77T+K142S, E77T+K142R,E77T+Q143R, E77T+N150T, E77T+N 150R, E77T+N150S, E77T+Q169A, E77T+Q169R,E77T+Q169K, E77T+H172R, E77T+Y174R, E77T+Y174L, E77T+Y174W, E77T+Y174F,E77T+R176Q, E77T+E177S, E77T+E177Y, E77T+N180R, E77T+P183T, E77T+P183G,E77T+Q184E, E77T+Q184K, E77T+R185G, E77T+Y196W, E77T+Y196F, E77T+N200T,E77T+S202R, E77T+Q203T, E77T+R205K, E77T+R210L, E77T+R210G, E77T+R210M,E77T+N213V, E77T+N213D, E77T+T228S, E77T+N229D, E77T+E234F, E77T+E234Y,E77T+A235K, E77T+A235R, E77T+S241C, E77T+Q243K, E77T+Q243E, E77T+R244K,E77T+R244V, E77T+A250G, E77T+K254Y, E77T+G257W, E77T+G257E, E77T+G257A,E77T+W260F, E77T+W260Y, E77T+W260L, E77T+W260T, E77T+Y262F, E77T+S266A,E77T+D268N, E77T+A270D, E77T+N272M, E77T+N272T, E77T+N273E, E77T+N273D,E77T+A276E, E77T+A276W, E77T+A276D, E77T+N279D, E77T+N279E, E77T+T280L,E77T+N283W, E77T+N283H, E77T+Y286W, E77T+Y286F, E77T+L288I, E77T+E290A,E77T+L294P, E77T+L294K, E77T+L294I, E77T+L294R, E77T+L294V, E77T+L294H,E77T+S295K, E77T+S295V, E77T+S295P, E77T+S295L, E77T+S295R, E77T+S295A,E77T+S295N, E77T+S295M, E77T+S295I, E77T+T296S, E77T+F298Y, E77N+D78G,E77N+H80K, E77N+V82R, E77N+V82I, E77N+V82S, E77N+A83P, E77N+A83S,E77N+Y93Q, E77N+Y93A, E77N+S95D, E77N+A97R, E77N+S98P, E77N+S98D,E77N+N100Y, E77N+D104A, E77N+D104G, E77N+E108S, E77N+S111A, E77N+S111 K,E77N+S111R, E77N+I114Q, E77N+I114M, E77N+I114W, E77N+K116R, E77N+D118K,E77N+T119R, E77N+S131T, E77N+E133R, E77N+E133Q, E77N+D135P, E77N+A136P,E77N+D139A, E77N+D139R, E77N+K142M, E77N+K142V, E77N+K142S, E77N+K142R,E77N+Q143R, E77N+N150T, E77N+N150R, E77N+N150S, E77N+Q169A, E77N+Q169R,E77N+Q169K, E77N+H172R, E77N+Y174R, E77N+Y174L, E77N+Y174W, E77N+Y174F,E77N+R176Q, E77N+E177S, E77N+E177Y, E77N+N180R, E77N+P183T, E77N+P183G,E77N+Q184E, E77N+Q184K, E77N+R185G, E77N+Y196W, E77N+Y196F, E77N+N200T,E77N+S202R, E77N+Q203T, E77N+R205K, E77N+R210L, E77N+R210G, E77N+R210M,E77N+N213V, E77N+N213D, E77N+T228S, E77N+N229D, E77N+E234F, E77N+E234Y,E77N+A235K, E77N+A235R, E77N+S241C, E77N+Q243K, E77N+Q243E, E77N+R244K,E77N+R244V, E77N+A250G, E77N+K254Y, E77N+G257W, E77N+G257E, E77N+G257A,E77N+W260F, E77N+W260Y, E77N+W260L, E77N+W260T, E77N+Y262F, E77N+S266A,E77N+D268N, E77N+A270D, E77N+N272M, E77N+N272T, E77N+N273E, E77N+N273D,E77N+A276E, E77N+A276W, E77N+A276D, E77N+N279D, E77N+N279E, E77N+T280L,E77N+N283W, E77N+N283H, E77N+Y286W, E77N+Y286F, E77N+L288I, E77N+E290A,E77N+L294P, E77N+L294K, E77N+L294I, E77N+L294R, E77N+L294V, E77N+L294H,E77N+S295K, E77N+S295V, E77N+S295P, E77N+S295L, E77N+S295R, E77N+S295A,E77N+S295N, E77N+S295M, E77N+S295I, E77N+T296S, E77N+F298Y, D78G+H80K,D78G+V82R, D78G+V82I, D78G+V82S, D78G+A83P, D78G+A83S, D78G+Y93Q,D78G+Y93A, D78G+S95D, D78G+A97R, D78G+S98P, D78G+S98D, D78G+N100Y,D78G+D104A, D78G+D104G, D78G+E108S, D78G+S111A, D78G+S111 K, D78G+S111R,D78G+I114Q, D78G+I114M, D78G+I114W, D78G+K116R, D78G+D118K, D78G+T119R,D78G+S131T, D78G+E133R, D78G+E133Q, D78G+D135P, D78G+A136P, D78G+D139A,D78G+D139R, D78G+K142M, D78G+K142V, D78G+K142S, D78G+K142R, D78G+Q143R,D78G+N150T, D78G+N150R, D78G+N150S, D78G+Q169A, D78G+Q169R, D78G+Q169K,D78G+H172R, D78G+Y174R, D78G+Y174L, D78G+Y174W, D78G+Y174F, D78G+R176Q,D78G+E177S, D78G+E177Y, D78G+N180R, D78G+P183T, D78G+P183G, D78G+Q184E,D78G+Q184K, D78G+R185G, D78G+Y196W, D78G+Y196F, D78G+N200T, D78G+S202R,D78G+Q203T, D78G+R205K, D78G+R210L, D78G+R210G, D78G+R210M, D78G+N213V,D78G+N213D, D78G+T228S, D78G+N229D, D78G+E234F, D78G+E234Y, D78G+A235K,D78G+A235R, D78G+S241C, D78G+Q243K, D78G+Q243E, D78G+R244K, D78G+R244V,D78G+A250G, D78G+K254Y, D78G+G257W, D78G+G257E, D78G+G257A, D78G+W260F,D78G+W260Y, D78G+W260L, D78G+W260T, D78G+Y262F, D78G+S266A, D78G+D268N,D78G+A270D, D78G+N272M, D78G+N272T, D78G+N273E, D78G+N273D, D78G+A276E,D78G+A276W, D78G+A276D, D78G+N279D, D78G+N279E, D78G+T280L, D78G+N283W,D78G+N283H, D78G+Y286W, D78G+Y286F, D78G+L288I, D78G+E290A, D78G+L294P,D78G+L294K, D78G+L294I, D78G+L294R, D78G+L294V, D78G+L294H, D78G+S295K,D78G+S295V, D78G+S295P, D78G+S295L, D78G+S295R, D78G+S295A, D78G+S295N,D78G+S295M, D78G+S295I, D78G+T296S, D78G+F298Y, H80K+V82R, H80K+V82I,H80K+V82S, H80K+A83P, H80K+A83S, H80K+Y93Q, H80K+Y93A, H80K+S95D,H80K+A97R, H80K+S98P, H80K+S98D, H80K+N100Y, H80K+D104A, H80K+D104G,H80K+E108S, H80K+S111A, H80K+S111K, H80K+S111R, H80K+I114Q, H80K+I114M,H80K+I114W, H80K+K116R, H80K+D118K, H80K+T119R, H80K+S131T, H80K+E133R,H80K+E133Q, H80K+D135P, H80K+A136P, H80K+D139A, H80K+D139R, H80K+K142M,H80K+K142V, H80K+K142S, H80K+K142R, H80K+Q143R, H80K+N150T, H80K+N150R,H80K+N150S, H80K+Q169A, H80K+Q169R, H80K+Q169K, H80K+H172R, H80K+Y174R,H80K+Y174L, H80K+Y174W, H80K+Y174F, H80K+R176Q, H80K+E177S, H80K+E177Y,H80K+N180R, H80K+P183T, H80K+P183G, H80K+Q184E, H80K+Q184K, H80K+R185G,H80K+Y196W, H80K+Y196F, H80K+N200T, H80K+S202R, H80K+Q203T, H80K+R205K,H80K+R210L, H80K+R210G, H80K+R210M, H80K+N213V, H80K+N213D, H80K+T228S,H80K+N229D, H80K+E234F, H80K+E234Y, H80K+A235K, H80K+A235R, H80K+S241C,H80K+Q243K, H80K+Q243E, H80K+R244K, H80K+R244V, H80K+A250G, H80K+K254Y,H80K+G257W, H80K+G257E, H80K+G257A, H80K+W260F, H80K+W260Y, H80K+W260L,H80K+W260T, H80K+Y262F, H80K+S266A, H80K+D268N, H80K+A270D, H80K+N272M,H80K+N272T, H80K+N273E, H80K+N273D, H80K+A276E, H80K+A276W, H80K+A276D,H80K+N279D, H80K+N279E, H80K+T280L, H80K+N283W, H80K+N283H, H80K+Y286W,H80K+Y286F, H80K+L288I, H80K+E290A, H80K+L294P, H80K+L294K, H80K+L294I,H80K+L294R, H80K+L294V, H80K+L294H, H80K+S295K, H80K+S295V, H80K+S295P,H80K+S295L, H80K+S295R, H80K+S295A, H80K+S295N, H80K+S295M, H80K+S295I,H80K+T296S, H80K+F298Y, V82R+A83P, V82R+A83S, V82R+Y93Q, V82R+Y93A,V82R+S95D, V82R+A97R, V82R+S98P, V82R+S98D, V82R+N100Y, V82R+D104A,V82R+D104G, V82R+E108S, V82R+S111A, V82R+S111K, V82R+S111R, V82R+I114Q,V82R+I114M, V82R+I114W, V82R+K116R, V82R+D118K, V82R+T119R, V82R+S131T,V82R+E133R, V82R+E133Q, V82R+D135P, V82R+A136P, V82R+D139A, V82R+D139R,V82R+K142M, V82R+K142V, V82R+K142S, V82R+K142R, V82R+Q143R, V82R+N150T,V82R+N150R, V82R+N150S, V82R+Q169A, V82R+Q169R, V82R+Q169K, V82R+H172R,V82R+Y174R, V82R+Y174L, V82R+Y174W, V82R+Y174F, V82R+R176Q, V82R+E177S,V82R+E177Y, V82R+N180R, V82R+P183T, V82R+P183G, V82R+Q184E, V82R+Q184K,V82R+R185G, V82R+Y196W, V82R+Y196F, V82R+N200T, V82R+S202R, V82R+Q203T,V82R+R205K, V82R+R210L, V82R+R210G, V82R+R210M, V82R+N213V, V82R+N213D,V82R+T228S, V82R+N229D, V82R+E234F, V82R+E234Y, V82R+A235K, V82R+A235R,V82R+S241C, V82R+Q243K, V82R+Q243E, V82R+R244K, V82R+R244V, V82R+A250G,V82R+K254Y, V82R+G257W, V82R+G257E, V82R+G257A, V82R+W260F, V82R+W260Y,V82R+W260L, V82R+W260T, V82R+Y262F, V82R+S266A, V82R+D268N, V82R+A270D,V82R+N272M, V82R+N272T, V82R+N273E, V82R+N273D, V82R+A276E, V82R+A276W,V82R+A276D, V82R+N279D, V82R+N279E, V82R+T280L, V82R+N283W, V82R+N283H,V82R+Y286W, V82R+Y286F, V82R+L288I, V82R+E290A, V82R+L294P, V82R+L294K,V82R+L294I, V82R+L294R, V82R+L294V, V82R+L294H, V82R+S295K, V82R+S295V,V82R+S295P, V82R+S295L, V82R+S295R, V82R+S295A, V82R+S295N, V82R+S295M,V82R+S295I, V82R+T296S, V82R+F298Y, V82I+A83P, V82I+A83S, V82I+Y93Q,V82+Y93A, V82I+S95D, V82I+A97R, V82I+S98P, V82I+S98D, V82I+N100Y,V82I+D104A, V82I+D104G, V82I+E108S, V82I+S111A, V82I+S111K, V82I+S111R,V82I+I114Q, V82I+I114M, V82I+I114W, V82I+K116R, V82I+D118K, V82I+T119R,V82I+S131T, V82I+E133R, V82I+E133Q, V82I+D135P, V82I+A136P, V82I+D139A,V82I+D139R, V82I+K142M, V82I+K142V, V82I+K142S, V82I+K142R, V82I+Q143R,V82I+N150T, V82I+N150R, V82I+N150S, V82I+Q169A, V82I+Q169R, V82I+Q169K,V82I+H172R, V82+Y174R, V82+Y174L, V82+Y174W, V82+Y174F, V82I+R176Q,V82I+E177S, V82I+E177Y, V82I+N180R, V82I+P183T, V82I+P183G, V82I+Q184E,V82I+Q184K, V82I+R185G, V82+Y196W, V82+Y196F, V82I+N200T, V82I+S202R,V82I+Q203T, V82I+R205K, V82I+R210L, V82I+R210G, V82I+R210M, V82I+N213V,V82I+N213D, V82I+T228S, V82I+N229D, V82I+E234F, V82I+E234Y, V82I+A235K,V82I+A235R, V82I+S241C, V82I+Q243K, V82I+Q243E, V82I+R244K, V82I+R244V,V82I+A250G, V82I+K254Y, V82I+G257W, V82I+G257E, V82I+G257A, V82I+W260F,V82I+W260Y, V82I+W260L, V82I+W260T, V82+Y262F, V82I+S266A, V82I+D268N,V82I+A270D, V82I+N272M, V82I+N272T, V82I+N273E, V82I+N273D, V82I+A276E,V82I+A276W, V82I+A276D, V82I+N279D, V82I+N279E, V82I+T280L, V82I+N283W,V82I+N283H, V82+Y286W, V82+Y286F, V82I+L288I, V82I+E290A, V82I+L294P,V82I+L294K, V82I+L294I, V82I+L294R, V82I+L294V, V82I+L294H, V82I+S295K,V82I+S295V, V82I+S295P, V82I+S295L, V82I+S295R, V82I+S295A, V82I+S295N,V82I+S295M, V82I+S295I, V82I+T296S, V82I+F298Y, V82S+A83P, V82S+A83S,V82S+Y93Q, V82S+Y93A, V82S+S95D, V82S+A97R, V82S+S98P, V82S+S98D,V82S+N100Y, V82S+D104A, V82S+D104G, V82S+E108S, V82S+S111A, V82S+S111 K,V82S+S111R, V82S+I114Q, V82S+I114M, V82S+I114W, V82S+K116R, V82S+D118K,V82S+T119R, V82S+S131T, V82S+E133R, V82S+E133Q, V82S+D135P, V82S+A136P,V82S+D139A, V82S+D139R, V82S+K142M, V82S+K142V, V82S+K142S, V82S+K142R,V82S+Q143R, V82S+N150T, V82S+N150R, V82S+N150S, V82S+Q169A, V82S+Q169R,V82S+Q169K, V82S+H172R, V82S+Y174R, V82S+Y174L, V82S+Y174W, V82S+Y174F,V82S+R176Q, V82S+E177S, V82S+E177Y, V82S+N180R, V82S+P183T, V82S+P183G,V82S+Q184E, V82S+Q184K, V82S+R185G, V82S+Y196W, V82S+Y196F, V82S+N200T,V82S+S202R, V82S+Q203T, V82S+R205K, V82S+R210L, V82S+R210G, V82S+R210M,V82S+N213V, V82S+N213D, V82S+T228S, V82S+N229D, V82S+E234F, V82S+E234Y,V82S+A235K, V82S+A235R, V82S+S241C, V82S+Q243K, V82S+Q243E, V82S+R244K,V82S+R244V, V82S+A250G, V82S+K254Y, V82S+G257W, V82S+G257E, V82S+G257A,V82S+W260F, V82S+W260Y, V82S+W260L, V82S+W260T, V82S+Y262F, V82S+S266A,V82S+D268N, V82S+A270D, V82S+N272M, V82S+N272T, V82S+N273E, V82S+N273D,V82S+A276E, V82S+A276W, V82S+A276D, V82S+N279D, V82S+N279E, V82S+T280L,V82S+N283W, V82S+N283H, V82S+Y286W, V82S+Y286F, V82S+L288I, V82S+E290A,V82S+L294P, V82S+L294K, V82S+L294I, V82S+L294R, V82S+L294V, V82S+L294H,V82S+S295K, V82S+S295V, V82S+S295P, V82S+S295L, V82S+S295R, V82S+S295A,V82S+S295N, V82S+S295M, V82S+S295I, V82S+T296S, V82S+F298Y, A83P+Y93Q,A83P+Y93A, A83P+S95D, A83P+A97R, A83P+S98P, A83P+S98D, A83P+N100Y,A83P+D104A, A83P+D104G, A83P+E108S, A83P+S111A, A83P+S111K, A83P+S111R,A83P+I114Q, A83P+I114M, A83P+I114W, A83P+K116R, A83P+D118K, A83P+T119R,A83P+S131T, A83P+E133R, A83P+E133Q, A83P+D135P, A83P+A136P, A83P+D139A,A83P+D139R, A83P+K142M, A83P+K142V, A83P+K142S, A83P+K142R, A83P+Q143R,A83P+N150T, A83P+N150R, A83P+N150S, A83P+Q169A, A83P+Q169R, A83P+Q169K,A83P+H172R, A83P+Y174R, A83P+Y174L, A83P+Y174W, A83P+Y174F, A83P+R176Q,A83P+E177S, A83P+E177Y, A83P+N180R, A83P+P183T, A83P+P183G, A83P+Q184E,A83P+Q184K, A83P+R185G, A83P+Y196W, A83P+Y196F, A83P+N200T, A83P+S202R,A83P+Q203T, A83P+R205K, A83P+R210L, A83P+R210G, A83P+R210M, A83P+N213V,A83P+N213D, A83P+T228S, A83P+N229D, A83P+E234F, A83P+E234Y, A83P+A235K,A83P+A235R, A83P+S241C, A83P+Q243K, A83P+Q243E, A83P+R244K, A83P+R244V,A83P+A250G, A83P+K254Y, A83P+G257W, A83P+G257E, A83P+G257A, A83P+W260F,A83P+W260Y, A83P+W260L, A83P+W260T, A83P+Y262F, A83P+S266A, A83P+D268N,A83P+A270D, A83P+N272M, A83P+N272T, A83P+N273E, A83P+N273D, A83P+A276E,A83P+A276W, A83P+A276D, A83P+N279D, A83P+N279E, A83P+T280L, A83P+N283W,A83P+N283H, A83P+Y286W, A83P+Y286F, A83P+L288I, A83P+E290A, A83P+L294P,A83P+L294K, A83P+L294I, A83P+L294R, A83P+L294V, A83P+L294H, A83P+S295K,A83P+S295V, A83P+S295P, A83P+S295L, A83P+S295R, A83P+S295A, A83P+S295N,A83P+S295M, A83P+S295I, A83P+T296S, A83P+F298Y, A83S+Y93Q, A83S+Y93A,A83S+S95D, A83S+A97R, A83S+S98P, A83S+S98D, A83S+N100Y, A83S+D104A,A83S+D104G, A83S+E108S, A83S+S111A, A83S+S111K, A83S+S111R, A83S+I114Q,A83S+I114M, A83S+I114W, A83S+K116R, A83S+D118K, A83S+T119R, A83S+S131T,A83S+E133R, A83S+E133Q, A83S+D135P, A83S+A136P, A83S+D139A, A83S+D139R,A83S+K142M, A83S+K142V, A83S+K142S, A83S+K142R, A83S+Q143R, A83S+N150T,A83S+N150R, A83S+N150S, A83S+Q169A, A83S+Q169R, A83S+Q169K, A83S+H172R,A83S+Y174R, A83S+Y174L, A83S+Y174W, A83S+Y174F, A83S+R176Q, A83S+E177S,A83S+E177Y, A83S+N180R, A83S+P183T, A83S+P183G, A83S+Q184E, A83S+Q184K,A83S+R185G, A83S+Y196W, A83S+Y196F, A83S+N200T, A83S+S202R, A83S+Q203T,A83S+R205K, A83S+R210L, A83S+R210G, A83S+R210M, A83S+N213V, A83S+N213D,A83S+T228S, A83S+N229D, A83S+E234F, A83S+E234Y, A83S+A235K, A83S+A235R,A83S+S241C, A83S+Q243K, A83S+Q243E, A83S+R244K, A83S+R244V, A83S+A250G,A83S+K254Y, A83S+G257W, A83S+G257E, A83S+G257A, A83S+W260F, A83S+W260Y,A83S+W260L, A83S+W260T, A83S+Y262F, A83S+S266A, A83S+D268N, A83S+A270D,A83S+N272M, A83S+N272T, A83S+N273E, A83S+N273D, A83S+A276E, A83S+A276W,A83S+A276D, A83S+N279D, A83S+N279E, A83S+T280L, A83S+N283W, A83S+N283H,A83S+Y286W, A83S+Y286F, A83S+L288I, A83S+E290A, A83S+L294P, A83S+L294K,A83S+L294I, A83S+L294R, A83S+L294V, A83S+L294H, A83S+S295K, A83S+S295V,A83S+S295P, A83S+S295L, A83S+S295R, A83S+S295A, A83S+S295N, A83S+S295M,A83S+S295I, A83S+T296S, A83S+F298Y, Y93Q+S95D, Y93Q+A97R, Y93Q+S98P,Y93Q+S98D, Y93Q+N100Y, Y93Q+D104A, Y93Q+D104G, Y93Q+E108S, Y93Q+S111A,Y93Q+S111 K, Y93Q+S111R, Y93Q+I114Q, Y93Q+I114M, Y93Q+I114W, Y93Q+K116R,Y93Q+D118K, Y93Q+T119R, Y93Q+S131T, Y93Q+E133R, Y93Q+E133Q, Y93Q+D135P,Y93Q+A136P, Y93Q+D139A, Y93Q+D139R, Y93Q+K142M, Y93Q+K142V, Y93Q+K142S,Y93Q+K142R, Y93Q+Q143R, Y93Q+N 150T, Y93Q+N150R, Y93Q+N150S, Y93Q+Q169A,Y93Q+Q169R, Y93Q+Q169K, Y93Q+H172R, Y93Q+Y174R, Y93Q+Y174L, Y93Q+Y174W,Y93Q+Y174F, Y93Q+R176Q, Y93Q+E177S, Y93Q+E177Y, Y93Q+N180R, Y93Q+P183T,Y93Q+P183G, Y93Q+Q184E, Y93Q+Q184K, Y93Q+R185G, Y93Q+Y196W, Y93Q+Y196F,Y93Q+N200T, Y93Q+S202R, Y93Q+Q203T, Y93Q+R205K, Y93Q+R210L, Y93Q+R210G,Y93Q+R210M, Y93Q+N213V, Y93Q+N213D, Y93Q+T228S, Y93Q+N229D, Y93Q+E234F,Y93Q+E234Y, Y93Q+A235K, Y93Q+A235R, Y93Q+S241C, Y93Q+Q243K, Y93Q+Q243E,Y93Q+R244 K, Y93Q+R244V, Y93Q+A250G, Y93Q+K254Y, Y93Q+G257W, Y93Q+G257E,Y93Q+G257A, Y93Q+W260F, Y93Q+W260Y, Y93Q+W260L, Y93Q+W260T, Y93Q+Y262F,Y93Q+S266A, Y93Q+D268N, Y93Q+A270D, Y93Q+N272M, Y93Q+N272T, Y93Q+N273E,Y93Q+N273D, Y93Q+A276E, Y93Q+A276W, Y93Q+A276D, Y93Q+N279D, Y93Q+N279E,Y93Q+T280L, Y93Q+N283W, Y93Q+N283H, Y93Q+Y286W, Y93Q+Y286F, Y93Q+L288I,Y93Q+E290A, Y93Q+L294P, Y93Q+L294K, Y93Q+L294I, Y93Q+L294R, Y93Q+L294V,Y93Q+L294H, Y93Q+S295K, Y93Q+S295V, Y93Q+S295P, Y93Q+S295L, Y93Q+S295R,Y93Q+S295A, Y93Q+S295N, Y93Q+S295M, Y93Q+S295I, Y93Q+T296S, Y93Q+F298Y,Y93A+S95D, Y93A+A97R, Y93A+S98P, Y93A+S98D, Y93A+N100Y, Y93A+D104A,Y93A+D104G, Y93A+E108S, Y93A+S111A, Y93A+S111K, Y93A+S111R, Y93A+I114Q,Y93A+I114M, Y93A+I114W, Y93A+K116R, Y93A+D118K, Y93A+T119R, Y93A+S131T,Y93A+E133R, Y93A+E133Q, Y93A+D135P, Y93A+A136P, Y93A+D139A, Y93A+D139R,Y93A+K142M, Y93A+K142V, Y93A+K142S, Y93A+K142R, Y93A+Q143R, Y93A+N150T,Y93A+N150R, Y93A+N150S, Y93A+Q169A, Y93A+Q169R, Y93A+Q169K, Y93A+H172R,Y93A+Y174R, Y93A+Y174L, Y93A+Y174W, Y93A+Y174F, Y93A+R176Q, Y93A+E177S,Y93A+E177Y, Y93A+N180R, Y93A+P183T, Y93A+P183G, Y93A+Q184E, Y93A+Q184K,Y93A+R185G, Y93A+Y196W, Y93A+Y196F, Y93A+N200T, Y93A+S202R, Y93A+Q203T,Y93A+R205K, Y93A+R210L, Y93A+R210G, Y93A+R210M, Y93A+N213V, Y93A+N213D,Y93A+T228S, Y93A+N229D, Y93A+E234F, Y93A+E234Y, Y93A+A235K, Y93A+A235R,Y93A+S241C, Y93A+Q243K, Y93A+Q243E, Y93A+R244 K, Y93A+R244V, Y93A+A250G,Y93A+K254Y, Y93A+G257W, Y93A+G257E, Y93A+G257A, Y93A+W260F, Y93A+W260Y,Y93A+W260L, Y93A+W260T, Y93A+Y262F, Y93A+S266A, Y93A+D268N, Y93A+A270D,Y93A+N272M, Y93A+N272T, Y93A+N273E, Y93A+N273D, Y93A+A276E, Y93A+A276W,Y93A+A276D, Y93A+N279D, Y93A+N279 E, Y93A+T280L, Y93A+N283W, Y93A+N283H,Y93A+Y286W, Y93A+Y286F, Y93A+L288I, Y93A+E290A, Y93A+L294P, Y93A+L294 K,Y93A+L294I, Y93A+L294R, Y93A+L294V, Y93A+L294H, Y93A+S295K, Y93A+S295V,Y93A+S295P, Y93A+S295L, Y93A+S295R, Y93A+S295A, Y93A+S295N, Y93A+S295M,Y93A+S295I, Y93A+T296S, Y93A+F298Y, S95D+A97R, S95D+S98P, S95D+S98D,S95D+N100Y, S95D+D104A, S95D+D104G, S95D+E108S, S95D+S111A, S95D+S111 K,S95D+S111R, S95D+I114Q, S95D+I114M, S95D+I114W, S95D+K116R, S95D+D118K,S95D+T119R, S95D+S131T, S95D+E133R, S95D+E133Q, S95D+D135P, S95D+A136P,S95D+D139A, S95D+D139R, S95D+K142M, S95D+K142V, S95D+K142S, S95D+K142R,S95D+Q143R, S95D+N150T, S95D+N150R, S95D+N150S, S95D+Q169A, S95D+Q169R,S95D+Q169K, S95D+H172R, S95D+Y174R, S95D+Y174L, S95D+Y174W, S95D+Y174F,S95D+R176Q, S95D+E177S, S95D+E177Y, S95D+N180R, S95D+P183T, S95D+P183G,S95D+Q184E, S95D+Q184K, S95D+R185G, S95D+Y196W, S95D+Y196F, S95D+N200T,S95D+S202R, S95D+Q203T, S95D+R205K, S95D+R210L, S95D+R210G, S95D+R210M,S95D+N213V, S95D+N213D, S95D+T228S, S95D+N229D, S95D+E234F, S95D+E234Y,S95D+A235K, S95D+A235R, S95D+S241C, S95D+Q243K, S95D+Q243E, S95D+R244K,S95D+R244V, S95D+A250G, S95D+K254Y, S95D+G257W, S95D+G257E, S95D+G257A,S95D+W260F, S95D+W260Y, S95D+W260L, S95D+W260T, S95D+Y262F, S95D+S266A,S95D+D268N, S95D+A270D, S95D+N272M, S95D+N272T, S95D+N273E, S95D+N273D,S95D+A276E, S95D+A276W, S95D+A276D, S95D+N279D, S95D+N279E, S95D+T280L,S95D+N283W, S95D+N283H, S95D+Y286W, S95D+Y286F, S95D+L288I, S95D+E290A,S95D+L294P, S95D+L294K, S95D+L294I, S95D+L294R, S95D+L294V, S95D+L294H,S95D+S295K, S95D+S295V, S95D+S295P, S95D+S295L, S95D+S295R, S95D+S295A,S95D+S295N, S95D+S295M, S95D+S295I, S95D+T296S, S95D+F298Y, A97R+S98P,A97R+S98D, A97R+N100Y, A97R+D104A, A97R+D104G, A97R+E108S, A97R+S111A,A97R+S111K, A97R+S111R, A97R+I114Q, A97R+I114M, A97R+I114W, A97R+K116R,A97R+D118K, A97R+T119R, A97R+S131T, A97R+E133R, A97R+E133Q, A97R+D135P,A97R+A136P, A97R+D139A, A97R+D139R, A97R+K142M, A97R+K142V, A97R+K142S,A97R+K142R, A97R+Q143R, A97R+N150T, A97R+N150R, A97R+N150S, A97R+Q169A,A97R+Q169R, A97R+Q169K, A97R+H172R, A97R+Y174R, A97R+Y174L, A97R+Y174W,A97R+Y174F, A97R+R176Q, A97R+E177S, A97R+E177Y, A97R+N180R, A97R+P183T,A97R+P183G, A97R+Q184E, A97R+Q184K, A97R+R185G, A97R+Y196W, A97R+Y196F,A97R+N200T, A97R+S202R, A97R+Q203T, A97R+R205K, A97R+R210L, A97R+R210G,A97R+R210M, A97R+N213V, A97R+N213D, A97R+T228S, A97R+N229D, A97R+E234F,A97R+E234Y, A97R+A235K, A97R+A235R, A97R+S241C, A97R+Q243K, A97R+Q243E,A97R+R244K, A97R+R244V, A97R+A250G, A97R+K254Y, A97R+G257W, A97R+G257E,A97R+G257A, A97R+W260F, A97R+W260Y, A97R+W260L, A97R+W260T, A97R+Y262F,A97R+S266A, A97R+D268N, A97R+A270D, A97R+N272M, A97R+N272T, A97R+N273E,A97R+N273D, A97R+A276E, A97R+A276W, A97R+A276D, A97R+N279D, A97R+N279E,A97R+T280L, A97R+N283W, A97R+N283H, A97R+Y286W, A97R+Y286F, A97R+L288I,A97R+E290A, A97R+L294P, A97R+L294K, A97R+L294I, A97R+L294R, A97R+L294V,A97R+L294H, A97R+S295K, A97R+S295V, A97R+S295P, A97R+S295L, A97R+S295R,A97R+S295A, A97R+S295N, A97R+S295M, A97R+S295I, A97R+T296S, A97R+F298Y,S98P+N100Y, S98P+D104A, S98P+D104G, S98P+E108S, S98P+S111A, S98P+S111 K,S98P+S111R, S98P+I114Q, S98P+I114M, S98P+I114W, S98P+K116R, S98P+D118K,S98P+T119R, S98P+S131T, S98P+E133R, S98P+E133Q, S98P+D135P, S98P+A136P,S98P+D139A, S98P+D139R, S98P+K142M, S98P+K142V, S98P+K142S, S98P+K142R,S98P+Q143R, S98P+N150T, S98P+N150R, S98P+N150S, S98P+Q169A, S98P+Q169R,S98P+Q169K, S98P+H172R, S98P+Y174R, S98P+Y174L, S98P+Y174W, S98P+Y174F,S98P+R176Q, S98P+E177S, S98P+E177Y, S98P+N180R, S98P+P183T, S98P+P183G,S98P+Q184E, S98P+Q184K, S98P+R185G, S98P+Y196W, S98P+Y196F, S98P+N200T,S98P+S202R, S98P+Q203T, S98P+R205K, S98P+R210L, S98P+R210G, S98P+R210M,S98P+N213V, S98P+N213D, S98P+T228S, S98P+N229D, S98P+E234F, S98P+E234Y,S98P+A235K, S98P+A235R, S98P+S241C, S98P+Q243K, S98P+Q243E, S98P+R244K,S98P+R244V, S98P+A250G, S98P+K254Y, S98P+G257W, S98P+G257E, S98P+G257A,S98P+W260F, S98P+W260Y, S98P+W260L, S98P+W260T, S98P+Y262F, S98P+S266A,S98P+D268N, S98P+A270D, S98P+N272M, S98P+N272T, S98P+N273E, S98P+N273D,S98P+A276E, S98P+A276W, S98P+A276D, S98P+N279D, S98P+N279E, S98P+T280L,S98P+N283W, S98P+N283H, S98P+Y286W, S98P+Y286F, S98P+L288I, S98P+E290A,S98P+L294P, S98P+L294K, S98P+L294I, S98P+L294R, S98P+L294V, S98P+L294H,S98P+S295K, S98P+S295V, S98P+S295P, S98P+S295L, S98P+S295R, S98P+S295A,S98P+S295N, S98P+S295M, S98P+S295I, S98P+T296S, S98P+F298Y, S98D+N100Y,S98D+D104A, S98D+D104G, S98D+E108S, S98D+S111A, S98D+S111K, S98D+S111R,S98D+I114Q, S98D+I114M, S98D+I114W, S98D+K116R, S98D+D118K, S98D+T119R,S98D+S131T, S98D+E133R, S98D+E133Q, S98D+D135P, S98D+A136P, S98D+D139A,S98D+D139R, S98D+K142M, S98D+K142V, S98D+K142S, S98D+K142R, S98D+Q143R,S98D+N150T, S98D+N150R, S98D+N150S, S98D+Q169A, S98D+Q169R, S98D+Q169K,S98D+H172R, S98D+Y174R, S98D+Y174L, S98D+Y174W, S98D+Y174F, S98D+R176Q,S98D+E177S, S98D+E177Y, S98D+N180R, S98D+P183T, S98D+P183G, S98D+Q184E,S98D+Q184K, S98D+R185G, S98D+Y196W, S98D+Y196F, S98D+N200T, S98D+S202R,S98D+Q203T, S98D+R205K, S98D+R210L, S98D+R210G, S98D+R210M, S98D+N213V,S98D+N213D, S98D+T228S, S98D+N229D, S98D+E234F, S98D+E234Y, S98D+A235K,S98D+A235R, S98D+S241C, S98D+Q243K, S98D+Q243E, S98D+R244K, S98D+R244V,S98D+A250G, S98D+K254Y, S98D+G257W, S98D+G257E, S98D+G257A, S98D+W260F,S98D+W260Y, S98D+W260L, S98D+W260T, S98D+Y262F, S98D+S266A, S98D+D268N,S98D+A270D, S98D+N272M, S98D+N272T, S98D+N273E, S98D+N273D, S98D+A276E,S98D+A276W, S98D+A276D, S98D+N279D, S98D+N279E, S98D+T280L, S98D+N283W,S98D+N283H, S98D+Y286W, S98D+Y286F, S98D+L288I, S98D+E290A, S98D+L294P,S98D+L294K, S98D+L294I, S98D+L294R, S98D+L294V, S98D+L294H, S98D+S295K,S98D+S295V, S98D+S295P, S98D+S295L, S98D+S295R, S98D+S295A, S98D+S295N,S98D+S295M, S98D+S295I, S98D+T296S, S98D+F298Y, N100Y+D104A,N100Y+D104G, N100Y+E108S, N100Y+S111A, N100Y+S111K, N100Y+S111R,N100Y+I114Q, N100Y+I114M, N100Y+I114W, N100Y+K116R, N100Y+D118K,N100Y+T119R, N100Y+S131T, N100Y+E133R, N100Y+E133Q, N100Y+D135P,N100Y+A136P, N100Y+D139A, N100Y+D139R, N100Y+K142M, N100Y+K142V,N100Y+K142S, N100Y+K142R, N100Y+Q143R, N100Y+N150T, N100Y+N150R,N100Y+N150S, N100Y+Q169A, N100Y+Q169R, N100Y+Q169K, N100Y+H172R,N100Y+Y174R, N100Y+Y174L, N100Y+Y174W, N100Y+Y174F, N100Y+R176Q,N100Y+E177S, N100Y+E177Y, N100Y+N180R, N100Y+P183T, N100Y+P183G,N100Y+Q184E, N100Y+Q184K, N100Y+R185G, N100Y+Y196W, N100Y+Y196F,N100Y+N200T, N100Y+S202R, N100Y+Q203T, N100Y+R205K, N100Y+R210L,N100Y+R210G, N100Y+R210M, N100Y+N213V, N100Y+N213D, N100Y+T228S,N100Y+N229D, N100Y+E234F, N 100Y+E234Y, N100Y+A235K, N100Y+A235R,N100Y+S241C, N100Y+Q243K, N100Y+Q243E, N 100Y+R244 K, N 100Y+R244V,N100Y+A250G, N100Y+K254Y, N100Y+G257W, N100Y+G257E, N100Y+G257A,N100Y+W260F, N100Y+W260Y, N100Y+W260L, N100Y+W260T, N100Y+Y262F,N100Y+S266A, N100Y+D268N, N100Y+A270D, N100Y+N272M, N100Y+N272T,N100Y+N273E, N100Y+N273D, N100Y+A276E, N100Y+A276W, N100Y+A276D, N100Y+N279 D, N 100Y+N279E, N100Y+T280L, N 100Y+N283W, N 100Y+N283H,N100Y+Y286W, N100Y+Y286F, N100Y+L288I, N100Y+E290A, N100Y+L294P,N100Y+L294K, N100Y+L294I, N100Y+L294R, N100Y+L294V, N100Y+L294H,N100Y+S295K, N100Y+S295V, N100Y+S295P, N100Y+S295L, N100Y+S295R,N100Y+S295A, N100Y+S295N, N100Y+S295M, N100Y+S295I, N100Y+T296S,N100Y+F298Y, D104A+E108S, D104A+S111A, D104A+S111K, D104A+S111R,D104A+I114Q, D104A+I114M, D104A+I114W, D104A+K116R, D104A+D118K,D104A+T119R, D104A+S131T, D104A+E133R, D104A+E133Q, D104A+D135P,D104A+A136P, D104A+D139A, D104A+D139R, D104A+K142M, D104A+K142V,D104A+K142S, D104A+K142R, D104A+Q143R, D104A+N150T, D104A+N150R,D104A+N150S, D104A+Q169A, D104A+Q169R, D104A+Q169K, D104A+H172R,D104A+Y174R, D104A+Y174L, D104A+Y174W, D104A+Y174F, D104A+R176Q,D104A+E177S, D104A+E177Y, D104A+N180R, D104A+P183T, D104A+P183G,D104A+Q184E, D104A+Q184K, D104A+R185G, D104A+Y196W, D104A+Y196F,D104A+N200T, D104A+S202R, D104A+Q203T, D104A+R205K, D104A+R210L,D104A+R210G, D104A+R210M, D104A+N213V, D104A+N213D, D104A+T228S,D104A+N229D, D104A+E234F, D104A+E234Y, D104A+A235K, D104A+A235R,D104A+S241C, D104A+Q243K, D104A+Q243E, D104A+R244 K, D104A+R244V,D104A+A250G, D104A+K254Y, D104A+G257W, D104A+G257E, D104A+G257A,D104A+W260F, D104A+W260Y, D104A+W260L, D104A+W260T, D104A+Y262F,D104A+S266A, D104A+D268N, D104A+A270D, D104A+N272M, D104A+N272T,D104A+N273 E, D104A+N273D, D104A+A276E, D104A+A276W, D104A+A276D,D104A+N279D, D104A+N279E, D104A+T280L, D104A+N283W, D104A+N283H,D104A+Y286W, D104A+Y286F, D104A+L288I, D104A+E290A, D104A+L294P,D104A+L294K, D104A+L294I, D104A+L294R, D104A+L294V, D104A+L294H,D104A+S295K, D104A+S295V, D104A+S295P, D104A+S295L, D104A+S295R,D104A+S295A, D104A+S295N, D104A+S295M, D104A+S295I, D104A+T296S,D104A+F298Y, D104G+E108S, D104G+S111A, D104G+S111K, D104G+S111R,D104G+I114Q, D104G+I114M, D104G+I114W, D104G+K116R, D104G+D118K,D104G+T119R, D104G+S131T, D104G+E133R, D104G+E133Q, D104G+D135P,D104G+A136P, D104G+D139A, D104G+D139R, D104G+K142M, D104G+K142V,D104G+K142S, D104G+K142R, D104G+Q143R, D104G+N150T, D104G+N150R,D104G+N150S, D104G+Q169A, D104G+Q169R, D104G+Q169K, D104G+H172R,D104G+Y174R, D104G+Y174L, D104G+Y174W, D104G+Y174F, D104G+R176Q,D104G+E177S, D104G+E177Y, D104G+N180R, D104G+P183T, D104G+P183G,D104G+Q184E, D104G+Q184K, D104G+R185G, D104G+Y196W, D104G+Y196F,D104G+N200T, D104G+S202R, D104G+Q203T, D104G+R205K, D104G+R210L,D104G+R210G, D104G+R210M, D104G+N213V, D104G+N213D, D104G+T228S,D104G+N229D, D104G+E234F, D104G+E234Y, D104G+A235K, D104G+A235R,D104G+S241C, D104G+Q243K, D104G+Q243E, D104G+R244K, D104G+R244V,D104G+A250G, D104G+K254Y, D104G+G257W, D104G+G257E, D104G+G257A,D104G+W260F, D104G+W260Y, D104G+W260L, D104G+W260T, D104G+Y262F,D104G+S266A, D104G+D268N, D104G+A270D, D104G+N272M, D104G+N272T,D104G+N273E, D104G+N273D, D104G+A276E, D104G+A276W, D104G+A276D,D104G+N279D, D104G+N279E, D104G+T280L, D104G+N283W, D104G+N283H,D104G+Y286W, D104G+Y286F, D104G+L288I, D104G+E290A, D104G+L294P,D104G+L294K, D104G+L294I, D104G+L294R, D104G+L294V, D104G+L294H,D104G+S295K, D104G+S295V, D104G+S295P, D104G+S295L, D104G+S295R,D104G+S295A, D104G+S295N, D104G+S295M, D104G+S295I, D104G+T296S,D104G+F298Y, E108S+S111A, E108S+S111K, E108S+S111R, E108S+I114Q,E108S+I114M, E108S+I114W, E108S+K116R, E108S+D118K, E108S+T119R,E108S+S131T, E108S+E133R, E108S+E133Q, E108S+D135P, E108S+A136P,E108S+D139A, E108S+D139R, E108S+K142M, E108S+K142V, E108S+K142S,E108S+K142R, E108S+Q143R, E108S+N150T, E108S+N150R, E108S+N150S,E108S+Q169A, E108S+Q169R, E108S+Q169K, E108S+H172R, E108S+Y174R,E108S+Y174L, E108S+Y174W, E108S+Y174F, E108S+R176Q, E108S+E177S,E108S+E177Y, E108S+N180R, E108S+P183T, E108S+P183G, E108S+Q184E,E108S+Q184K, E108S+R185G, E108S+Y196W, E108S+Y196F, E108S+N200T,E108S+S202R, E108S+Q203T, E108S+R205K, E108S+R210L, E108S+R210G,E108S+R210M, E108S+N213V, E108S+N213D, E108S+T228S, E108S+N229D,E108S+E234F, E108S+E234Y, E108S+A235K, E108S+A235R, E108S+S241C,E108S+Q243K, E108S+Q243E, E108S+R244K, E108S+R244V, E108S+A250G,E108S+K254Y, E108S+G257W, E108S+G257E, E108S+G257A, E108S+W260F,E108S+W260Y, E108S+W260L, E108S+W260T, E108S+Y262F, E108S+S266A,E108S+D268N, E108S+A270D, E108S+N272M, E108S+N272T, E108S+N273E,E108S+N273D, E108S+A276E, E108S+A276W, E108S+A276D, E108S+N279D,E108S+N279E, E108S+T280L, E108S+N283W, E108S+N283H, E108S+Y286W,E108S+Y286F, E108S+L288I, E108S+E290A, E108S+L294P, E108S+L294K,E108S+L294I, E108S+L294R, E108S+L294V, E108S+L294H, E108S+S295K,E108S+S295V, E108S+S295P, E108S+S295L, E108S+S295R, E108S+S295A,E108S+S295N, E108S+S295M, E108S+S295I, E108S+T296S, E108S+F298Y,S111A+I114Q, S111A+I114M, S111A+I114W, S111A+K116R, S111A+D118K,S111A+T119R, S111A+S131T, S111A+E133R, S111A+E133Q, S111A+D135P,S111A+A136P, S111A+D139A, S111A+D139R, S111A+K142M, S111A+K142V,S111A+K142S, S111A+K142R, S111A+Q143R, S111A+N150T, S111A+N150R,S111A+N150S, S111A+Q169A, S111A+Q169R, S111A+Q169K, S111A+H172R,S111A+Y174R, S111A+Y174L, S111A+Y174W, S111A+Y174F, S111A+R176Q,S111A+E177S,S111A+E177Y,S111A+N180R,S111A+P183T,S111A+P183G,S111A+Q184E,S111A+Q184K, S111A+R185G, S111A+Y196W, S111A+Y196F, S111A+N200T,S111A+S202R, S111A+Q203T, S111A+R205K, S111A+R210L, S111A+R210G,S111A+R210M, S111A+N213V, S111A+N213D, S111A+T228S, S111A+N229D,S111A+E234F, S111A+E234Y, S111A+A235K, S111A+A235R, S111A+S241C,S111A+Q243K, S111A+Q243E, S111A+R244K, S111A+R244V, S111A+A250G,S111A+K254Y, S111A+G257W, S111A+G257E, S111A+G257A, S111A+W260F,S111A+W260Y, S111A+W260L, S111A+W260T, S111A+Y262F, S111A+S266A,S111A+D268N, S111A+A270D, S111A+N272M, S111A+N272T, S111A+N273E,S111A+N273D, S111A+A276E, S111A+A276W, S111A+A276D, S111A+N279D,S111A+N279E, S111A+T280L, S111A+N283W, S111A+N283H, S111A+Y286W,S111A+Y286F, S111A+L288I, S111A+E290A, S111A+L294P, S111A+L294K,S111A+L294I, S111A+L294R, S111A+L294V, S111A+L294H, S111A+S295K,S111A+S295V, S111A+S295P, S111A+S295L, S111A+S295R, S111A+S295A,S111A+S295N, S111A+S295M, S111A+S295I, S111A+T296S, S111A+F298Y,S111K+I114Q, S111K+I114M, S111K+I114W, S111K+K116R, S111K+D118K,S111K+T119R, S111K+S131T, S111K+E133R, S111K+E133Q, S111K+D135P,S111K+A136P, S111K+D139A, S111K+D139R, S111K+K142M, S111K+K142V,S111K+K142S, S111K+K142R, S111K+Q143R, S111K+N150T, S111K+N150R,S111K+N150S, S111K+Q169A, S111K+Q169R, S111K+Q169K, S111K+H172R,S111K+Y174R, S111K+Y174L, S111K+Y174W, S111K+Y174F, S111K+R176Q,S111K+E177S, S111K+E177Y, S111K+N180R, S111K+P183T, S111K+P183G,S111K+Q184E, S111K+Q184K, S111K+R185G, S111K+Y196W, S111K+Y196F,S111K+N200T, S111K+S202R, S111K+Q203T, S111K+R205K, S111K+R210L,S111K+R210G, S111K+R210M, S111K+N213V, S111K+N213D, S111K+T228S,S111K+N229D, S111K+E234F, S111K+E234Y, S111K+A235K, S111K+A235R,S111K+S241C, S111K+Q243K, S111K+Q243E, S111K+R244K, S111K+R244V,S111K+A250G, S111K+K254Y, S111K+G257W, S111K+G257E, S111K+G257A,S111K+W260F, S111K+W260Y, S111K+W260L, S111K+W260T, S111K+Y262F,S111K+S266A, S111K+D268N, S111K+A270D, S111K+N272M, S111K+N272T,S111K+N273E, S111K+N273D, S111K+A276E, S111K+A276W, S111K+A276D,S111K+N279D, S111K+N279E, S111K+T280L, S111K+N283W, S111 K+N283H,S111K+Y286W, S111K+Y286F, S111K+L288I, S111K+E290A, S111K+L294P,S111K+L294K, S111K+L294I, S111K+L294R, S111K+L294V, S111K+L294H,S111K+S295K, S111K+S295V, S111K+S295P, S111K+S295L, S111K+S295R,S111K+S295A, S111K+S295N, S111K+S295M, S111K+S295I, S111K+T296S,S111K+F298Y, S111R+I114Q, S111R+I114M, S111R+I114W, S111R+K116R,S111R+D118K, S111R+T119R, S111R+S131T, S111R+E133R, S111R+E133Q,S111R+D135P, S111R+A136P, S111R+D139A, S111R+D139R, S111R+K142M,S111R+K142V, S111R+K142S, S111R+K142R, S111R+Q143R, S111R+N150T,S111R+N150R, S111R+N150S, S111R+Q169A, S111R+Q169R, S111R+Q169K,S111R+H172R, S111R+Y174R, S111R+Y174L, S111R+Y174W, S111R+Y174F,S111R+R176Q, S111R+E177S, S111R+E177Y, S111R+N180R, S111R+P183T,S111R+P183G, S111R+Q184E, S111R+Q184K, S111R+R185G, S111R+Y196W,S111R+Y196F, S111R+N200T, S111R+S202R, S111R+Q203T, S111R+R205K,S111R+R210L, S111R+R210G, S111R+R210M, S111R+N213V, S111R+N213D,S111R+T228S, S111R+N229D, S111R+E234F, S111R+E234Y, S111R+A235K,S111R+A235R, S111R+S241C, S111R+Q243K, S111R+Q243E, S111R+R244K,S111R+R244V, S111R+A250G, S111 R+K254Y, S111R+G257W, S111R+G257E,S111R+G257A, S111R+W260F, S111R+W260Y, S111R+W260L, S111R+W260T,S111R+Y262F, S111R+S266A, S111R+D268N, S111R+A270D, S111R+N272M,S111R+N272T, S111R+N273E, S111R+N273D, S111R+A276E, S111R+A276W,S111R+A276D, S111R+N279D, S111R+N279E, S111R+T280L, S111R+N283W,S111R+N283H, S111R+Y286W, S111R+Y286F, S111R+L288I, S111R+E290A,S111R+L294P, S111R+L294K, S111R+L294I, S111R+L294R, S111R+L294V,S111R+L294H, S111R+S295K, S111R+S295V, S111R+S295P, S111R+S295L, S111R+S295R, S111R+S295A, S111R+S295N, S111 R+S295M, S111 R+S295I,S111R+T296S, S111R+F298Y, I114Q+K116R, I114Q+D118K, I114Q+T119R,I114Q+S131T, I114Q+E133R, I114Q+E133Q, I114Q+D135P, I114Q+A136P,I114Q+D139A, I114Q+D139R, I114Q+K142M, I114Q+K142V, I114Q+K142S,I114Q+K142R, I114Q+Q143R, I114Q+N150T, I114Q+N150R, I114Q+N150S,I114Q+Q169A, I114Q+Q169R, I114Q+Q169K, I114Q+H172R, I114Q+Y174R,I114Q+Y174L, I114Q+Y174W, I114Q+Y174F, I114Q+R176Q, I114Q+E177S,I114Q+E177Y, I114Q+N180R, I114Q+P183T, I114Q+P183G, I114Q+Q184E,I114Q+Q184K, I114Q+R185G, I114Q+Y196W, I114Q+Y196F, I114Q+N200T,I114Q+S202R, I114Q+Q203T, I114Q+R205K, I114Q+R210L, I114Q+R210G,I114Q+R210M, I114Q+N213V, I114Q+N213D, I114Q+T228S, I114Q+N229D,I114Q+E234F, I114Q+E234Y, I114Q+A235K, I114Q+A235R, I114Q+S241C,I114Q+Q243K, I114Q+Q243E, I114Q+R244K, I114Q+R244V, I114Q+A250G,I114Q+K254Y, I114Q+G257W, I114Q+G257E, I114Q+G257A, I114Q+W260F,I114Q+W260Y, I114Q+W260L, I114Q+W260T, I114Q+Y262F, I114Q+S266A,I114Q+D268N, I114Q+A270D, I114Q+N272M, I114Q+N272T, I114Q+N273E,I114Q+N273D, I114Q+A276E, I114Q+A276W, I114Q+A276D, I114Q+N279D,I114Q+N279E, I114Q+T280L, I114Q+N283W, I114Q+N283H, I114Q+Y286W,I114Q+Y286F, I114Q+L288I, I114Q+E290A, I114Q+L294P, I114Q+L294K,I114Q+L294I, I114Q+L294R, I114Q+L294V, I114Q+L294H, I114Q+S295K,I114Q+S295V, I114Q+S295P, I114Q+S295L, I114Q+S295R, I114Q+S295A,I114Q+S295N, I114Q+S295M, I114Q+S295I, I114Q+T296S, I114Q+F298Y,I114M+K116R, I114M+D118K, I114M+T119R, I114M+S131T, I114M+E133R,I114M+E133Q, I114M+D135P, I114M+A136P, I114M+D139A, I114M+D139R,I114M+K142M, I114M+K142V, I114M+K142S, I114M+K142R, I114M+Q143R,I114M+N150T, I114M+N150R, I114M+N150S, I114M+Q169A, I114M+Q169R,I114M+Q169K, I114M+H172R, I114M+Y174R, I114M+Y174L, I114M+Y174W,I114M+Y174F, I114M+R176Q, I114M+E177S, I114M+E177Y, I114M+N180R,I114M+P183T, I114M+P183G, I114M+Q184E, I114M+Q184K, I114M+R185G,I114M+Y196W, I114M+Y196F, I114M+N200T, I114M+S202R, I114M+Q203T,I114M+R205K, I114M+R210L, I114M+R210G, I114M+R210M, I114M+N213V,I114M+N213D, I114M+T228S, I114M+N229D, I114M+E234F, I114M+E234Y,I114M+A235K, I114M+A235R, I114M+S241C, I114M+Q243K, I114M+Q243E,I114M+R244K, I114M+R244V, I114M+A250G, I114M+K254Y, I114M+G257W,I114M+G257E, I114M+G257A, I114M+W260F, I114M+W260Y, I114M+W260L,I114M+W260T, I114M+Y262F, I114M+S266A, I114M+D268N, I114M+A270D,I114M+N272M, I114M+N272T, I114M+N273E, I114M+N273D, I114M+A276E,I114M+A276W, I114M+A276D, I114M+N279D, I114M+N279E, I114M+T280L,I114M+N283W, I114M+N283H, I114M+Y286W, I114M+Y286F, I114M+L288I,I114M+E290A, I114M+L294P, I114M+L294K, I114M+L294I, I114M+L294R,I114M+L294V, I114M+L294H, I114M+S295K, I114M+S295V, I114M+S295P,I114M+S295L, I114M+S295R, I114M+S295A, I114M+S295N, I114M+S295M,I114M+S295I, I114M+T296S, I114M+F298Y, I114W+K116R, I114W+D118K,I114W+T119R, I114W+S131T, I114W+E133R, I114W+E133Q, I114W+D135P,I114W+A136P, I114W+D139A, I114W+D139R, I114W+K142M, I114W+K142V,I114W+K142S, I114W+K142R, I114W+Q143R, I114W+N150T, I114W+N150R,I114W+N150S, I114W+Q169A, I114W+Q169R, I114W+Q169K, I114W+H172R,I114W+Y174R, I114W+Y174L, I114W+Y174W, I114W+Y174F, I114W+R176Q,I114W+E177S, I114W+E177Y, I114W+N180R, I114W+P183T, I114W+P183G,I114W+Q184E, I114W+Q184K, I114W+R185G, I114W+Y196W, I114W+Y196F,I114W+N200T, I114W+S202R, I114W+Q203T, I114W+R205K, I114W+R210L,I114W+R210G, I114W+R210M, I114W+N213V, I114W+N213D, I114W+T228S,I114W+N229D, I114W+E234F, I114W+E234Y, I114W+A235K, I114W+A235R,I114W+S241C, I114W+Q243K, I114W+Q243E, I114W+R244K, I114W+R244V,I114W+A250G, I114W+K254Y, I114W+G257W, I114W+G257E, I114W+G257A,I114W+W260F, I114W+W260Y, I114W+W260L, I114W+W260T, I114W+Y262F,I114W+S266A, I114W+D268N, I114W+A270D, I114W+N272M, I114W+N272T,I114W+N273E, I114W+N273D, I114W+A276E, I114W+A276W, I114W+A276D,I114W+N279D, I114W+N279E, I114W+T280L, I114W+N283W, I114W+N283H,I114W+Y286W, I114W+Y286F, I114W+L288I, I114W+E290A, I114W+L294P,I114W+L294K, I114W+L294I, I114W+L294R, I114W+L294V, I114W+L294H,I114W+S295K, I114W+S295V, I114W+S295P, I114W+S295L, I114W+S295R,I114W+S295A, I114W+S295N, I114W+S295M, I114W+S295I, I114W+T296S,I114W+F298Y, K116R+D118K, K116R+T119R, K116R+S131T, K116R+E133R,K116R+E133Q, K116R+D135P, K116R+A136P, K116R+D139A, K116R+D139R,K116R+K142M, K116R+K142V, K116R+K142S, K116R+K142R, K116R+Q143R,K116R+N150T, K116R+N150R, K116R+N150S, K116R+Q169A, K116R+Q169R,K116R+Q169K, K116R+H172R, K116R+Y174R, K116R+Y174L, K116R+Y174W,K116R+Y174F, K116R+R176Q, K116R+E177S, K116R+E177Y, K116R+N180R,K116R+P183T, K116R+P183G, K116R+Q184E, K116R+Q184K, K116R+R185G,K116R+Y196W, K116R+Y196F, K116R+N200T, K116R+S202R, K116R+Q203T,K116R+R205K, K116R+R210L, K116R+R210G, K116R+R210M, K116R+N213V,K116R+N213D, K116R+T228S, K116R+N229D, K116R+E234F, K116R+E234Y,K116R+A235K, K116R+A235R, K116R+S241C, K116R+Q243K, K116R+Q243E,K116R+R244K, K116R+R244V, K116R+A250G, K116R+K254Y, K116R+G257W,K116R+G257E, K116R+G257A, K116R+W260F, K116R+W260Y, K116R+W260L,K116R+W260T, K116R+Y262F, K116R+S266A, K116R+D268N, K116R+A270D,K116R+N272M, K116R+N272T, K116R+N273E, K116R+N273D, K116R+A276E,K116R+A276W, K116R+A276D, K116R+N279D, K116R+N279E, K116R+T280L,K116R+N283W, K116R+N283H, K116R+Y286W, K116R+Y286F, K116R+L288I,K116R+E290A, K116R+L294P, K116R+L294K, K116R+L294I, K116R+L294R,K116R+L294V, K116R+L294H, K116R+S295K, K116R+S295V, K116R+S295P,K116R+S295L, K116R+S295R, K116R+S295A, K116R+S295N, K116R+S295M,K116R+S295I, K116R+T296S, K116R+F298Y, D118K+T119R, D118K+S131T,D118K+E133R, D118K+E133Q, D118K+D135P, D118K+A136P, D118K+D139A,D118K+D139R, D118K+K142M, D118K+K142V, D118K+K142S, D118K+K142R,D118K+Q143R, D118K+N150T, D118K+N150R, D118K+N150S, D118K+Q169A,D118K+Q169R, D118K+Q169K, D118K+H172R, D118K+Y174R, D118K+Y174L,D118K+Y174W, D118K+Y174F, D118K+R176Q, D118K+E177S, D118K+E177Y,D118K+N180R, D118K+P183T, D118K+P183G, D118K+Q184E, D118K+Q184K,D118K+R185G, D118K+Y196W, D118K+Y196F, D118K+N200T, D118K+S202R,D118K+Q203T, D118K+R205K, D118K+R210L, D118K+R210G, D118K+R210M,D118K+N213V, D118K+N213D, D118K+T228S, D118K+N229D, D118K+E234F,D118K+E234Y, D118K+A235K, D118K+A235R, D118K+S241C, D118K+Q243K,D118K+Q243E, D118K+R244K, D118K+R244V, D118K+A250G, D118K+K254Y,D118K+G257W, D118K+G257E, D118K+G257A, D118K+W260F, D118K+W260Y,D118K+W260L, D118K+W260T, D118K+Y262F, D118K+S266A, D118K+D268N,D118K+A270D, D118K+N272M, D118K+N272T, D118K+N273E, D118K+N273D,D118K+A276E, D118K+A276W, D118K+A276D, D118K+N279D, D118K+N279E,D118K+T280L, D118K+N283W, D118K+N283H, D118K+Y286W, D118K+Y286F,D118K+L288I, D118K+E290A, D118K+L294P, D118K+L294K, D118K+L294I,D118K+L294R, D118K+L294V, D118K+L294H, D118K+S295K, D118K+S295V,D118K+S295P, D118K+S295L, D118K+S295R, D118K+S295A, D118K+S295N,D118K+S295M, D118K+S295I, D118K+T296S, D118K+F298Y, T119R+S131T,T119R+E133R, T119R+E133Q, T119R+D135P, T119R+A136P, T119R+D139A,T119R+D139R, T119R+K142M, T119R+K142V, T119R+K142S, T119R+K142R,T119R+Q143R, T119R+N150T, T119R+N150R, T119R+N150S, T119R+Q169A,T119R+Q169R, T119R+Q169K, T119R+H172R, T119R+Y174R, T119R+Y174L,T119R+Y174W, T119R+Y174F, T119R+R176Q, T119R+E177S, T119R+E177Y,T119R+N180R, T119R+P183T, T119R+P183G, T119R+Q184E, T119R+Q184K,T119R+R185G, T119R+Y196W, T119R+Y196F, T119R+N200T, T119R+S202R,T119R+Q203T, T119R+R205K, T119R+R210L, T119R+R210G, T119R+R210M,T119R+N213V, T119R+N213D, T119R+T228S, T119R+N229D, T119R+E234F,T119R+E234Y, T119R+A235K, T119R+A235R, T119R+S241C, T119R+Q243K,T119R+Q243E, T119R+R244K, T119R+R244V, T119R+A250G, T119R+K254Y,T119R+G257W, T119R+G257E, T119R+G257A, T119R+W260F, T119R+W260Y,T119R+W260L, T119R+W260T, T119R+Y262F, T119R+S266A, T119R+D268N,T119R+A270D, T119R+N272M, T119R+N272T, T119R+N273E, T119R+N273D,T119R+A276E, T119R+A276W, T119R+A276D, T119R+N279D, T119R+N279E,T119R+T280L, T119R+N283W, T119R+N283H, T119R+Y286W, T119R+Y286F,T119R+L288I, T119R+E290A, T119R+L294P, T119R+L294K, T119R+L294I,T119R+L294R, T119R+L294V, T119R+L294H, T119R+S295K, T119R+S295V,T119R+S295P, T119R+S295L, T119R+S295R, T119R+S295A, T119R+S295N,T119R+S295M, T119R+S295I, T119R+T296S, T119R+F298Y, S131T+E133R,S131T+E133Q, S131T+D135P, S131T+A136P, S131T+D139A, S131T+D139R,S131T+K142M, S131T+K142V, S131T+K142S, S131T+K142R, S131T+Q143R,S131T+N150T, S131T+N150R, S131T+N150S, S131T+Q169A, S131T+Q169R,S131T+Q169K, S131T+H172R, S131T+Y174R, S131T+Y174L, S131T+Y174W,S131T+Y174F, S131T+R176Q, S131T+E177S, S131T+E177Y, S131T+N180R,S131T+P183T, S131T+P183G, S131T+Q184E, S131T+Q184K, S131T+R185G,S131T+Y196W, S131T+Y196F, S131T+N200T, S131T+S202R, S131T+Q203T,S131T+R205K, S131T+R210L, S131T+R210G, S131T+R210M, S131T+N213V,S131T+N213D, S131T+T228S, S131T+N229D, S131T+E234F, S131T+E234Y,S131T+A235K, S131T+A235R, S131T+S241C, S131T+Q243K, S131T+Q243E,S131T+R244K, S131T+R244V, S131T+A250G, S131T+K254Y, S131T+G257W,S131T+G257E, S131T+G257A, S131T+W260F, S131T+W260Y, S131T+W260L,S131T+W260T, S131T+Y262F, S131T+S266A, S131T+D268N, S131T+A270D,S131T+N272M, S131T+N272T, S131T+N273E, S131T+N273D, S131T+A276E,S131T+A276W, S131T+A276D, S131T+N279D, S131T+N279E, S131T+T280L,S131T+N283W, S131T+N283H, S131T+Y286W, S131T+Y286F, S131T+L288I,S131T+E290A, S131T+L294P, S131T+L294K, S131T+L294I, S131T+L294R,S131T+L294V, S131T+L294H, S131T+S295K, S131T+S295V, S131T+S295P,S131T+S295L, S131T+S295R, S131T+S295A, S131T+S295N, S131T+S295M,S131T+S295I, S131T+T296S, S131T+F298Y, E133R+D135P, E133R+A136P,E133R+D139A, E133R+D139R, E133R+K142M, E133R+K142V, E133R+K142S,E133R+K142R, E133R+Q143R, E133R+N150T, E133R+N150R, E133R+N150S,E133R+Q169A, E133R+Q169R, E133R+Q169K, E133R+H172R, E133R+Y174R,E133R+Y174L, E133R+Y174W, E133R+Y174F, E133R+R176Q, E133R+E177S,E133R+E177Y, E133R+N180R, E133R+P183T, E133R+P183G, E133R+Q184E,E133R+Q184K, E133R+R185G, E133R+Y196W, E133R+Y196F, E133R+N200T,E133R+S202R, E133R+Q203T, E133R+R205K, E133R+R210L, E133R+R210G,E133R+R210M, E133R+N213V, E133R+N213D, E133R+T228S, E133R+N229D,E133R+E234F, E133R+E234Y, E133R+A235K, E133R+A235R, E133R+S241C,E133R+Q243K, E133R+Q243E, E133R+R244K, E133R+R244V, E133R+A250G,E133R+K254Y, E133R+G257W, E133R+G257E, E133R+G257A, E133R+W260F,E133R+W260Y, E133R+W260L, E133R+W260T, E133R+Y262F, E133R+S266A,E133R+D268N, E133R+A270D, E133R+N272M, E133R+N272T, E133R+N273E,E133R+N273D, E133R+A276E, E133R+A276W, E133R+A276D, E133R+N279D,E133R+N279E, E133R+T280L, E133R+N283W, E133R+N283H, E133R+Y286W,E133R+Y286F, E133R+L288I, E133R+E290A, E133R+L294P, E133R+L294K,E133R+L294I, E133R+L294R, E133R+L294V, E133R+L294H, E133R+S295K,E133R+S295V, E133R+S295P, E133R+S295L, E133R+S295R, E133R+S295A,E133R+S295N, E133R+S295M, E133R+S295I, E133R+T296S, E133R+F298Y,E133Q+D135P, E133Q+A136P, E133Q+D139A, E133Q+D139R, E133Q+K142M,E133Q+K142V, E133Q+K142S, E133Q+K142R, E133Q+Q143R, E133Q+N150T,E133Q+N150R, E133Q+N150S, E133Q+Q169A, E133Q+Q169R, E133Q+Q169K,E133Q+H172R, E133Q+Y174R, E133Q+Y174L, E133Q+Y174W, E133Q+Y174F,E133Q+R176Q, E133Q+E177S, E133Q+E177Y, E133Q+N180R, E133Q+P183T,E133Q+P183G, E133Q+Q184E, E133Q+Q184K, E133Q+R185G, E133Q+Y196W,E133Q+Y196F, E133Q+N200T, E133Q+S202R, E133Q+Q203T, E133Q+R205K,E133Q+R210L, E133Q+R210G, E133Q+R210M, E133Q+N213V, E133Q+N213D,E133Q+T228S, E133Q+N229D, E133Q+E234F, E133Q+E234Y, E133Q+A235K,E133Q+A235R, E133Q+S241C, E133Q+Q243K, E133Q+Q243E, E133Q+R244K,E133Q+R244V, E133Q+A250G, E133Q+K254Y, E133Q+G257W, E133Q+G257E,E133Q+G257A, E133Q+W260F, E133Q+W260Y, E133Q+W260L, E133Q+W260T,E133Q+Y262F, E133Q+S266A, E133Q+D268N, E133Q+A270D, E133Q+N272M,E133Q+N272T, E133Q+N273E, E133Q+N273D, E133Q+A276E, E133Q+A276W,E133Q+A276D, E133Q+N279D, E133Q+N279E, E133Q+T280L, E133Q+N283W,E133Q+N283H, E133Q+Y286W, E133Q+Y286F, E133Q+L288I, E133Q+E290A,E133Q+L294P, E133Q+L294K, E133Q+L294I, E133Q+L294R, E133Q+L294V,E133Q+L294H, E133Q+S295K, E133Q+S295V, E133Q+S295P, E133Q+S295L,E133Q+S295R, E133Q+S295A, E133Q+S295N, E133Q+S295M, E133Q+S295I,E133Q+T296S, E133Q+F298Y, D135P+A136P, D135P+D139A, D135P+D139R,D135P+K142M, D135P+K142V, D135P+K142S, D135P+K142R, D135P+Q143R,D135P+N150T, D135P+N150R, D135P+N150S, D135P+Q169A, D135P+Q169R,D135P+Q169K, D135P+H172R, D135P+Y174R, D135P+Y174L, D135P+Y174W,D135P+Y174F, D135P+R176Q, D135P+E177S, D135P+E177Y, D135P+N180R,D135P+P183T, D135P+P183G, D135P+Q184E, D135P+Q184K, D135P+R185G,D135P+Y196W, D135P+Y196F, D135P+N200T, D135P+S202R, D135P+Q203T,D135P+R205K, D135P+R210L, D135P+R210G, D135P+R210M, D135P+N213V,D135P+N213D, D135P+T228S, D135P+N229D, D135P+E234F, D135P+E234Y,D135P+A235K, D135P+A235R, D135P+S241C, D135P+Q243K, D135P+Q243E,D135P+R244K, D135P+R244V, D135P+A250G, D135P+K254Y, D135P+G257W,D135P+G257E, D135P+G257A, D135P+W260F, D135P+W260Y, D135P+W260L,D135P+W260T, D135P+Y262F, D135P+S266A, D135P+D268N, D135P+A270D,D135P+N272M, D135P+N272T, D135P+N273E, D135P+N273D, D135P+A276E,D135P+A276W, D135P+A276D, D135P+N279D, D135P+N279E, D135P+T280L,D135P+N283W, D135P+N283H, D135P+Y286W, D135P+Y286F, D135P+L288I,D135P+E290A, D135P+L294P, D135P+L294K, D135P+L294I, D135P+L294R,D135P+L294V, D135P+L294H, D135P+S295K, D135P+S295V, D135P+S295P,D135P+S295L, D135P+S295R, D135P+S295A, D135P+S295N, D135P+S295M,D135P+S295I, D135P+T296S, D135P+F298Y, A136P+D139A, A136P+D139R,A136P+K142M, A136P+K142V, A136P+K142S, A136P+K142R, A136P+Q143R,A136P+N150T, A136P+N150R, A136P+N150S, A136P+Q169A, A136P+Q169R,A136P+Q169K, A136P+H172R, A136P+Y174R, A136P+Y174L, A136P+Y174W,A136P+Y174F, A136P+R176Q, A136P+E177S, A136P+E177Y, A136P+N180R,A136P+P183T, A136P+P183G, A136P+Q184E, A136P+Q184K, A136P+R185G,A136P+Y196W, A136P+Y196F, A136P+N200T, A136P+S202R, A136P+Q203T,A136P+R205K, A136P+R210L, A136P+R210G, A136P+R210M, A136P+N213V,A136P+N213D, A136P+T228S, A136P+N229D, A136P+E234F, A136P+E234Y,A136P+A235K, A136P+A235R, A136P+S241C, A136P+Q243K, A136P+Q243E,A136P+R244K, A136P+R244V, A136P+A250G, A136P+K254Y, A136P+G257W,A136P+G257E, A136P+G257A, A136P+W260F, A136P+W260Y, A136P+W260L,A136P+W260T, A136P+Y262F, A136P+S266A, A136P+D268N, A136P+A270D,A136P+N272M, A136P+N272T, A136P+N273E, A136P+N273D, A136P+A276E,A136P+A276W, A136P+A276D, A136P+N279D, A136P+N279E, A136P+T280L,A136P+N283W, A136P+N283H, A136P+Y286W, A136P+Y286F, A136P+L288I,A136P+E290A, A136P+L294P, A136P+L294K, A136P+L294I, A136P+L294R,A136P+L294V, A136P+L294H, A136P+S295K, A136P+S295V, A136P+S295P,A136P+S295L, A136P+S295R, A136P+S295A, A136P+S295N, A136P+S295M,A136P+S295I, A136P+T296S, A136P+F298Y, D139A+K142M, D139A+K142V,D139A+K142S, D139A+K142R, D139A+Q143R, D139A+N150T, D139A+N150R,D139A+N150S, D139A+Q169A, D139A+Q169R, D139A+Q169K, D139A+H172R,D139A+Y174R, D139A+Y174L, D139A+Y174W, D139A+Y174F, D139A+R176Q,D139A+E177S, D139A+E177Y, D139A+N180R, D139A+P183T, D139A+P183G,D139A+Q184E, D139A+Q184K, D139A+R185G, D139A+Y196W, D139A+Y196F,D139A+N200T, D139A+S202R, D139A+Q203T, D139A+R205K, D139A+R210L,D139A+R210G, D139A+R210M, D139A+N213V, D139A+N213D, D139A+T228S,D139A+N229D, D139A+E234F, D139A+E234Y, D139A+A235K, D139A+A235R,D139A+S241C, D139A+Q243K, D139A+Q243E, D139A+R244K, D139A+R244V,D139A+A250G, D139A+K254Y, D139A+G257W, D139A+G257E, D139A+G257A,D139A+W260F, D139A+W260Y, D139A+W260L, D139A+W260T, D139A+Y262F,D139A+S266A, D139A+D268N, D139A+A270D, D139A+N272M, D139A+N272T,D139A+N273E, D139A+N273D, D139A+A276E, D139A+A276W, D139A+A276D,D139A+N279D, D139A+N279E, D139A+T280L, D139A+N283W, D139A+N283H,D139A+Y286W, D139A+Y286F, D139A+L288I, D139A+E290A, D139A+L294P,D139A+L294K, D139A+L294I, D139A+L294R, D139A+L294V, D139A+L294H,D139A+S295K, D139A+S295V, D139A+S295P, D139A+S295L, D139A+S295R,D139A+S295A, D139A+S295N, D139A+S295M, D139A+S295I, D139A+T296S,D139A+F298Y, D139R+K142M, D139R+K142V, D139R+K142S, D139R+K142R,D139R+Q143R, D139R+N150T, D139R+N150R, D139R+N150S, D139R+Q169A,D139R+Q169R, D139R+Q169K, D139R+H172R, D139R+Y174R, D139R+Y174L,D139R+Y174W, D139R+Y174F, D139R+R176Q, D139R+E177S, D139R+E177Y,D139R+N180R, D139R+P183T, D139R+P183G, D139R+Q184E, D139R+Q184K,D139R+R185G, D139R+Y196W, D139R+Y196F, D139R+N200T, D139R+S202R,D139R+Q203T, D139R+R205K, D139R+R210L, D139R+R210G, D139R+R210M,D139R+N213V, D139R+N213D, D139R+T228S, D139R+N229D, D139R+E234F,D139R+E234Y, D139R+A235K, D139R+A235R, D139R+S241C, D139R+Q243K,D139R+Q243E, D139R+R244K, D139R+R244V, D139R+A250G, D139R+K254Y,D139R+G257W, D139R+G257E, D139R+G257A, D139R+W260F, D139R+W260Y,D139R+W260L, D139R+W260T, D139R+Y262F, D139R+S266A, D139R+D268N,D139R+A270D, D139R+N272M, D139R+N272T, D139R+N273E, D139R+N273D,D139R+A276E, D139R+A276W, D139R+A276D, D139R+N279D, D139R+N279E,D139R+T280L, D139R+N283W, D139R+N283H, D139R+Y286W, D139R+Y286F,D139R+L288I, D139R+E290A, D139R+L294P, D139R+L294K, D139R+L294I,D139R+L294R, D139R+L294V, D139R+L294H, D139R+S295K, D139R+S295V,D139R+S295P, D139R+S295L, D139R+S295R, D139R+S295A, D139R+S295N,D139R+S295M, D139R+S295I, D139R+T296S, D139R+F298Y, K142M+Q143R,K142M+N150T, K142M+N150R, K142M+N150S, K142M+Q169A, K142M+Q169R,K142M+Q169K, K142M+H172R, K142M+Y174R, K142M+Y174L, K142M+Y174W,K142M+Y174F, K142M+R176Q, K142M+E177S, K142M+E177Y, K142M+N180R,K142M+P183T, K142M+P183G, K142M+Q184E, K142M+Q184K, K142M+R185G,K142M+Y196W, K142M+Y196F, K142M+N200T, K142M+S202R, K142M+Q203T,K142M+R205K, K142M+R210L, K142M+R210G, K142M+R210M, K142M+N213V,K142M+N213D, K142M+T228S, K142M+N229D, K142M+E234F, K142M+E234Y,K142M+A235K, K142M+A235R, K142M+S241C, K142M+Q243K, K142M+Q243E,K142M+R244K, K142M+R244V, K142M+A250G, K142M+K254Y, K142M+G257W,K142M+G257E, K142M+G257A, K142M+W260F, K142M+W260Y, K142M+W260L,K142M+W260T, K142M+Y262F, K142M+S266A, K142M+D268N, K142M+A270D,K142M+N272M, K142M+N272T, K142M+N273E, K142M+N273D, K142M+A276E,K142M+A276W, K142M+A276D, K142M+N279D, K142M+N279E, K142M+T280L,K142M+N283W, K142M+N283H, K142M+Y286W, K142M+Y286F, K142M+L288I,K142M+E290A, K142M+L294P, K142M+L294K, K142M+L294I, K142M+L294R,K142M+L294V, K142M+L294H, K142M+S295K, K142M+S295V, K142M+S295P,K142M+S295L, K142M+S295R, K142M+S295A, K142M+S295N, K142M+S295M,K142M+S295I, K142M+T296S, K142M+F298Y, K142V+Q143R, K142V+N150T,K142V+N150R, K142V+N150S, K142V+Q169A, K142V+Q169R, K142V+Q169K,K142V+H172R, K142V+Y174R, K142V+Y174L, K142V+Y174W, K142V+Y174F,K142V+R176Q, K142V+E177S, K142V+E177Y, K142V+N180R, K142V+P183T,K142V+P183G, K142V+Q184E, K142V+Q184K, K142V+R185G, K142V+Y196W,K142V+Y196F, K142V+N200T, K142V+S202R, K142V+Q203T, K142V+R205K,K142V+R210L, K142V+R210G, K142V+R210M, K142V+N213V, K142V+N213D,K142V+T228S, K142V+N229D, K142V+E234F, K142V+E234Y, K142V+A235K,K142V+A235R, K142V+S241C, K142V+Q243K, K142V+Q243E, K142V+R244K,K142V+R244V, K142V+A250G, K142V+K254Y, K142V+G257W, K142V+G257E,K142V+G257A, K142V+W260F, K142V+W260Y, K142V+W260L, K142V+W260T,K142V+Y262F, K142V+S266A, K142V+D268N, K142V+A270D, K142V+N272M,K142V+N272T, K142V+N273E, K142V+N273D, K142V+A276E, K142V+A276W,K142V+A276D, K142V+N279D, K142V+N279E, K142V+T280L, K142V+N283W,K142V+N283H, K142V+Y286W, K142V+Y286F, K142V+L288I, K142V+E290A,K142V+L294P, K142V+L294K, K142V+L294I, K142V+L294R, K142V+L294V,K142V+L294H, K142V+S295K, K142V+S295V, K142V+S295P, K142V+S295L,K142V+S295R, K142V+S295A, K142V+S295N, K142V+S295M, K142V+S295I,K142V+T296S, K142V+F298Y, K142S+Q143R, K142S+N150T, K142S+N150R,K142S+N150S, K142S+Q169A, K142S+Q169R, K142S+Q169K, K142S+H172R,K142S+Y174R, K142S+Y174L, K142S+Y174W, K142S+Y174F, K142S+R176Q,K142S+E177S, K142S+E177Y, K142S+N180R, K142S+P183T, K142S+P183G,K142S+Q184E, K142S+Q184K, K142S+R185G, K142S+Y196W, K142S+Y196F,K142S+N200T, K142S+S202R, K142S+Q203T, K142S+R205K, K142S+R210L,K142S+R210G, K142S+R210M, K142S+N213V, K142S+N213D, K142S+T228S,K142S+N229D, K142S+E234F, K142S+E234Y, K142S+A235K, K142S+A235R,K142S+S241C, K142S+Q243K, K142S+Q243E, K142S+R244K, K142S+R244V,K142S+A250G, K142S+K254Y, K142S+G257W, K142S+G257E, K142S+G257A,K142S+W260F, K142S+W260Y, K142S+W260L, K142S+W260T, K142S+Y262F,K142S+S266A, K142S+D268N, K142S+A270D, K142S+N272M, K142S+N272T,K142S+N273E, K142S+N273D, K142S+A276E, K142S+A276W, K142S+A276D,K142S+N279D, K142S+N279E, K142S+T280L, K142S+N283W, K142S+N283H,K142S+Y286W, K142S+Y286F, K142S+L288I, K142S+E290A, K142S+L294P,K142S+L294K, K142S+L294I, K142S+L294R, K142S+L294V, K142S+L294H,K142S+S295K, K142S+S295V, K142S+S295P, K142S+S295L, K142S+S295R,K142S+S295A, K142S+S295N, K142S+S295M, K142S+S295I, K142S+T296S,K142S+F298Y, K142R+Q143R, K142R+N150T, K142R+N150R, K142R+N150S,K142R+Q169A, K142R+Q169R, K142R+Q169K, K142R+H172R, K142R+Y174R,K142R+Y174L, K142R+Y174W, K142R+Y174F, K142R+R176Q, K142R+E177S,K142R+E177Y, K142R+N180R, K142R+P183T, K142R+P183G, K142R+Q184E,K142R+Q184K, K142R+R185G, K142R+Y196W, K142R+Y196F, K142R+N200T,K142R+S202R, K142R+Q203T, K142R+R205K, K142R+R210L, K142R+R210G,K142R+R210M, K142R+N213V, K142R+N213D, K142R+T228S, K142R+N229D,K142R+E234F, K142R+E234Y, K142R+A235K, K142R+A235R, K142R+S241C,K142R+Q243K, K142R+Q243E, K142R+R244K, K142R+R244V, K142R+A250G,K142R+K254Y, K142R+G257W, K142R+G257E, K142R+G257A, K142R+W260F,K142R+W260Y, K142R+W260L, K142R+W260T, K142R+Y262F, K142R+S266A,K142R+D268N, K142R+A270D, K142R+N272M, K142R+N272T, K142R+N273E,K142R+N273D, K142R+A276E, K142R+A276W, K142R+A276D, K142R+N279D,K142R+N279E, K142R+T280L, K142R+N283W, K142R+N283H, K142R+Y286W,K142R+Y286F, K142R+L288I, K142R+E290A, K142R+L294P, K142R+L294K,K142R+L294I, K142R+L294R, K142R+L294V, K142R+L294H, K142R+S295K,K142R+S295V, K142R+S295P, K142R+S295L, K142R+S295R, K142R+S295A,K142R+S295N, K142R+S295M, K142R+S295I, K142R+T296S, K142R+F298Y,Q143R+N150T, Q143R+N150R, Q143R+N150S, Q143R+Q169A, Q143R+Q169R,Q143R+Q169K, Q143R+H172R, Q143R+Y174R, Q143R+Y174L, Q143R+Y174W,Q143R+Y174F, Q143R+R176Q, Q143R+E177S, Q143R+E177Y, Q143R+N180R,Q143R+P183T, Q143R+P183G, Q143R+Q184E, Q143R+Q184K, Q143R+R185G,Q143R+Y196W, Q143R+Y196F, Q143R+N200T, Q143R+S202R, Q143R+Q203T,Q143R+R205K, Q143R+R210L, Q143R+R210G, Q143R+R210M, Q143R+N213V,Q143R+N213D, Q143R+T228S, Q143R+N229D, Q143R+E234F, Q143R+E234Y,Q143R+A235K, Q143R+A235R, Q143R+S241C, Q143R+Q243K, Q143R+Q243E,Q143R+R244K, Q143R+R244V, Q143R+A250G, Q143R+K254Y, Q143R+G257W,Q143R+G257E, Q143R+G257A, Q143R+W260F, Q143R+W260Y, Q143R+W260L,Q143R+W260T, Q143R+Y262F, Q143R+S266A, Q143R+D268N, Q143R+A270D,Q143R+N272M, Q143R+N272T, Q143R+N273E, Q143R+N273D, Q143R+A276E,Q143R+A276W, Q143R+A276D, Q143R+N279D, Q143R+N279E, Q143R+T280L,Q143R+N283W, Q143R+N283H, Q143R+Y286W, Q143R+Y286F, Q143R+L288I,Q143R+E290A, Q143R+L294P, Q143R+L294K, Q143R+L294I, Q143R+L294R,Q143R+L294V, Q143R+L294H, Q143R+S295K, Q143R+S295V, Q143R+S295P,Q143R+S295L, Q143R+S295R, Q143R+S295A, Q143R+S295N, Q143R+S295M,Q143R+S295I, Q143R+T296S, Q143R+F298Y, N150T+Q169A, N150T+Q169R,N150T+Q169K, N150T+H172R, N150T+Y174R, N150T+Y174L, N150T+Y174W,N150T+Y174F, N150T+R176Q, N150T+E177S, N150T+E177Y, N150T+N180R,N150T+P183T, N150T+P183G, N150T+Q184E, N150T+Q184K, N150T+R185G,N150T+Y196W, N150T+Y196F, N150T+N200T, N150T+S202R, N150T+Q203T,N150T+R205K, N150T+R210L, N150T+R210G, N150T+R210M, N150T+N213V,N150T+N213D, N150T+T228S, N150T+N229D, N150T+E234F, N150T+E234Y,N150T+A235K, N150T+A235R, N150T+S241C, N150T+Q243K, N150T+Q243E,N150T+R244K, N150T+R244V, N150T+A250G, N150T+K254Y, N150T+G257W,N150T+G257E, N150T+G257A, N150T+W260F, N150T+W260Y, N150T+W260L,N150T+W260T, N150T+Y262F, N150T+S266A, N150T+D268N, N150T+A270D,N150T+N272M, N150T+N272T, N150T+N273E, N150T+N273D, N150T+A276E,N150T+A276W, N150T+A276D, N150T+N279D, N150T+N279E, N150T+T280L,N150T+N283W, N150T+N283H, N150T+Y286W, N150T+Y286F, N150T+L288I,N150T+E290A, N150T+L294P, N150T+L294K, N150T+L294I, N150T+L294R,N150T+L294V, N150T+L294H, N150T+S295K, N150T+S295V, N150T+S295P,N150T+S295L, N150T+S295R, N150T+S295A, N150T+S295N, N150T+S295M,N150T+S295I, N150T+T296S, N150T+F298Y, N150R+Q169A, N150R+Q169R,N150R+Q169K, N150R+H172R, N150R+Y174R, N150R+Y174L, N150R+Y174W,N150R+Y174F, N150R+R176Q, N150R+E177S, N150R+E177Y, N150R+N180R,N150R+P183T, N150R+P183G, N150R+Q184E, N150R+Q184K, N150R+R185G,N150R+Y196W, N150R+Y196F, N150R+N200T, N150R+S202R, N150R+Q203T,N150R+R205K, N150R+R210L, N150R+R210G, N150R+R210M, N150R+N213V,N150R+N213D, N150R+T228S, N150R+N229D, N150R+E234F, N150R+E234Y,N150R+A235K, N150R+A235R, N150R+S241C, N 150 R+Q243 K, N 150 R+Q243 E, N150R+R244K, N150R+R244V, N150R+A250G, N150R+K254Y, N150R+G257W,N150R+G257E, N150R+G257A, N150R+W260F, N 150 R+W260Y, N150R+W260L,N150R+W260T, N150R+Y262F, N150R+S266A, N150R+D268N, N150R+A270D,N150R+N272M, N150R+N272T, N150R+N273E, N150R+N273D, N150R+A276E,N150R+A276W, N150R+A276D, N150R+N279D, N150R+N279E, N150R+T280L,N150R+N283W, N150R+N283H, N150R+Y286W, N150R+Y286F, N150R+L288I,N150R+E290A, N150R+L294P, N150R+L294K, N150R+L294I, N150R+L294R,N150R+L294V, N150R+L294H, N150R+S295K, N150R+S295V, N150R+S295P,N150R+S295L, N150R+S295R, N150R+S295A, N150R+S295N, N150R+S295M,N150R+S295I, N150R+T296S, N150R+F298Y, N150S+Q169A, N150S+Q169R,N150S+Q169K, N150S+H172R, N150S+Y174R, N150S+Y174L, N150S+Y174W,N150S+Y174F, N150S+R176Q, N150S+E177S, N150S+E177Y, N150S+N180R,N150S+P183T, N150S+P183G, N150S+Q184E, N150S+Q184K, N150S+R185G,N150S+Y196W, N150S+Y196F, N150S+N200T, N150S+S202R, N150S+Q203T,N150S+R205K, N150S+R210L, N150S+R210G, N150S+R210M, N150S+N213V,N150S+N213D, N150S+T228S, N150S+N229D, N150S+E234F, N150S+E234Y,N150S+A235K, N150S+A235R, N150S+S241C, N150S+Q243K, N150S+Q243E,N150S+R244K, N150S+R244V, N150S+A250G, N150S+K254Y, N150S+G257W,N150S+G257E, N150S+G257A, N150S+W260F, N150S+W260Y, N150S+W260L,N150S+W260T, N150S+Y262F, N150S+S266A, N150S+D268N, N150S+A270D,N150S+N272M, N150S+N272T, N150S+N273E, N150S+N273D, N150S+A276E,N150S+A276W, N150S+A276D, N150S+N279D, N150S+N279E, N150S+T280L,N150S+N283W, N150S+N283H, N150S+Y286W, N150S+Y286F, N150S+L288I,N150S+E290A, N150S+L294P, N150S+L294K, N150S+L294I, N150S+L294R,N150S+L294V, N150S+L294H, N150S+S295K, N150S+S295V, N150S+S295P,N150S+S295L, N150S+S295R, N150S+S295A, N150S+S295N, N150S+S295M,N150S+S295I, N150S+T296S, N150S+F298Y, Q169A+H172R, Q169A+Y174R,Q169A+Y174L, Q169A+Y174W, Q169A+Y174F, Q169A+R176Q, Q169A+E177S,Q169A+E177Y, Q169A+N180R, Q169A+P183T, Q169A+P183G, Q169A+Q184E,Q169A+Q184K, Q169A+R185G, Q169A+Y196W, Q169A+Y196F, Q169A+N200T,Q169A+S202R, Q169A+Q203T, Q169A+R205K, Q169A+R210L, Q169A+R210G,Q169A+R210M, Q169A+N213V, Q169A+N213D, Q169A+T228S, Q169A+N229D,Q169A+E234F, Q169A+E234Y, Q169A+A235K, Q169A+A235R, Q169A+S241C,Q169A+Q243K, Q169A+Q243E, Q 169A+R244 K, Q 169A+R244V, Q169A+A250G, Q169A+K254Y, Q169A+G257W, Q169A+G257E, Q169A+G257A, Q169A+W260F,Q169A+W260Y, Q169A+W260L, Q169A+W260T, Q169A+Y262F, Q169A+S266A, Q169A+D268N, Q169A+A270D, Q169A+N272M, Q169A+N272T, Q169A+N273E,Q169A+N273D, Q169A+A276E, Q169A+A276W, Q169A+A276D, Q169A+N279D,Q169A+N279E, Q169A+T280L, Q169A+N283W, Q169A+N283H, Q169A+Y286W,Q169A+Y286F, Q169A+L288I, Q169A+E290A, Q169A+L294P, Q169A+L294K,Q169A+L294I, Q169A+L294R, Q169A+L294V, Q169A+L294H, Q169A+S295K,Q169A+S295V, Q169A+S295P, Q169A+S295L, Q169A+S295R, Q169A+S295A,Q169A+S295N, Q169A+S295M, Q169A+S295I, Q169A+T296S, Q169A+F298Y,Q169R+H172R, Q169R+Y174R, Q169R+Y174L, Q169R+Y174W, Q169R+Y174F,Q169R+R176Q, Q169R+E177S, Q169R+E177Y, Q169R+N180R, Q169R+P183T,Q169R+P183G, Q169R+Q184E, Q169R+Q184K, Q169R+R185G, Q169R+Y196W,Q169R+Y196F, Q169R+N200T, Q169R+S202R, Q169R+Q203T, Q169R+R205K,Q169R+R210L, Q169R+R210G, Q169R+R210M, Q169R+N213V, Q169R+N213D,Q169R+T228S, Q169R+N229D, Q169R+E234F, Q169R+E234Y, Q169R+A235K,Q169R+A235R, Q169R+S241C, Q169R+Q243K, Q169R+Q243E, Q169R+R244K,Q169R+R244V, Q169R+A250G, Q169R+K254Y, Q169R+G257W, Q169R+G257E,Q169R+G257A, Q169R+W260F, Q169R+W260Y, Q169R+W260L, Q169R+W260T,Q169R+Y262F, Q169R+S266A, Q169R+D268N, Q169R+A270D, Q169R+N272M,Q169R+N272T, Q169R+N273E, Q169R+N273D, Q169R+A276E, Q169R+A276W,Q169R+A276D, Q169R+N279D, Q169R+N279E, Q169R+T280L, Q169R+N283W,Q169R+N283H, Q169R+Y286W, Q169R+Y286F, Q169R+L288I, Q169R+E290A,Q169R+L294P, Q169R+L294K, Q169R+L294I, Q169R+L294R, Q169R+L294V,Q169R+L294H, Q169R+S295K, Q169R+S295V, Q169R+S295P, Q169R+S295L,Q169R+S295R, Q169R+S295A, Q169R+S295N, Q169R+S295M, Q169R+S295I,Q169R+T296S, Q169R+F298Y, Q169K+H172R, Q169K+Y174R, Q169K+Y174L,Q169K+Y174W, Q169K+Y174F, Q169K+R176Q, Q169K+E177S, Q169K+E177Y,Q169K+N180R, Q169K+P183T, Q169K+P183G, Q169K+Q184E, Q169K+Q184K,Q169K+R185G, Q169K+Y196W, Q169K+Y196F, Q169K+N200T, Q169K+S202R,Q169K+Q203T, Q169K+R205K, Q169K+R210L, Q169K+R210G, Q169K+R210M,Q169K+N213V, Q169K+N213D, Q169K+T228S, Q169K+N229D, Q169K+E234F,Q169K+E234Y, Q169K+A235K, Q169K+A235R, Q169K+S241C, Q169K+Q243K,Q169K+Q243E, Q169K+R244K, Q169K+R244V, Q169K+A250G, Q169K+K254Y,Q169K+G257W, Q169K+G257E, Q169K+G257A, Q169K+W260F, Q169K+W260Y,Q169K+W260L, Q169K+W260T, Q169K+Y262F, Q169K+S266A, Q169K+D268N,Q169K+A270D, Q169K+N272M, Q169K+N272T, Q169K+N273E, Q169K+N273D,Q169K+A276E, Q169K+A276W, Q169K+A276D, Q169K+N279D, Q169K+N279E,Q169K+T280L, Q169K+N283W, Q169K+N283H, Q169K+Y286W, Q169K+Y286F,Q169K+L288I, Q169K+E290A, Q169K+L294P, Q169K+L294K, Q169K+L294I,Q169K+L294R, Q169K+L294V, Q169K+L294H, Q169K+S295K, Q169K+S295V,Q169K+S295P, Q169K+S295L, Q169K+S295R, Q169K+S295A, Q169K+S295N,Q169K+S295M, Q169K+S295I, Q169K+T296S, Q169K+F298Y, H172R+Y174R,H172R+Y174L, H172R+Y174W, H172R+Y174F, H172R+R176Q, H172R+E177S,H172R+E177Y, H172R+N180R, H172R+P183T, H172R+P183G, H172R+Q184E,H172R+Q184K, H172R+R185G, H172R+Y196W, H172R+Y196F, H172R+N200T,H172R+S202R, H172R+Q203T, H172R+R205K, H172R+R210L, H172R+R210G,H172R+R210M, H172R+N213V, H172R+N213D, H172R+T228S, H172R+N229D,H172R+E234F, H172R+E234Y, H172R+A235K, H172R+A235R, H172R+S241C,H172R+Q243K, H172R+Q243E, H172R+R244K, H172R+R244V, H172R+A250G,H172R+K254Y, H172R+G257W, H172R+G257E, H172R+G257A, H172R+W260F,H172R+W260Y, H172R+W260L, H172R+W260T, H172R+Y262F, H172R+S266A,H172R+D268N, H172R+A270D, H172R+N272M, H172R+N272T, H172R+N273E,H172R+N273D, H172R+A276E, H172R+A276W, H172R+A276D, H172R+N279D,H172R+N279E, H172R+T280L, H172R+N283W, H172R+N283H, H172R+Y286W,H172R+Y286F, H172R+L288I, H172R+E290A, H172R+L294P, H172R+L294K,H172R+L294I, H172R+L294R, H172R+L294V, H172R+L294H, H172R+S295K,H172R+S295V, H172R+S295P, H172R+S295L, H172R+S295R, H172R+S295A,H172R+S295N, H172R+S295M, H172R+S295I, H172R+T296S, H172R+F298Y,Y174R+R176Q, Y174R+E177S, Y174R+E177Y, Y174R+N180R, Y174R+P183T,Y174R+P183G, Y174R+Q184E, Y174R+Q184K, Y174R+R185G, Y174R+Y196W,Y174R+Y196F, Y174R+N200T, Y174R+S202R, Y174R+Q203T, Y174R+R205K,Y174R+R210L, Y174R+R210G, Y174R+R210M, Y174R+N213V, Y174R+N213D,Y174R+T228S, Y174R+N229D, Y174R+E234F, Y174R+E234Y, Y174R+A235K,Y174R+A235R, Y174R+S241C, Y174R+Q243K, Y174R+Q243E, Y174R+R244K,Y174R+R244V, Y174R+A250G, Y174R+K254Y, Y174R+G257W, Y174R+G257E,Y174R+G257A, Y174R+W260F, Y174R+W260Y, Y174R+W260L, Y174R+W260T,Y174R+Y262F, Y174R+S266A, Y174R+D268N, Y174R+A270D, Y174R+N272M,Y174R+N272T, Y174R+N273E, Y174R+N273D, Y174R+A276E, Y174R+A276W,Y174R+A276D, Y174R+N279D, Y174R+N279E, Y174R+T280L, Y174R+N283W,Y174R+N283H, Y174R+Y286W, Y174R+Y286F, Y174R+L288I, Y174R+E290A,Y174R+L294P, Y174R+L294K, Y174R+L294I, Y174R+L294R, Y174R+L294V,Y174R+L294H, Y174R+S295K, Y174R+S295V, Y174R+S295P, Y174R+S295L, Y174R+S295R, Y174R+S295A, Y174 R+S295N, Y174R+S295M, Y174R+S295I,Y174R+T296S, Y174R+F298Y, Y174L+R176Q, Y174L+E177S, Y174L+E177Y,Y174L+N180R, Y174L+P183T, Y174L+P183G, Y174L+Q184E, Y174L+Q184K,Y174L+R185G, Y174L+Y196W, Y174L+Y196F, Y174L+N200T, Y174L+S202R,Y174L+Q203T, Y174L+R205K, Y174L+R210L, Y174L+R210G, Y174L+R210M,Y174L+N213V, Y174L+N213D, Y174L+T228S, Y174L+N229D, Y174L+E234F,Y174L+E234Y, Y174L+A235K, Y174L+A235R, Y174L+S241C, Y174L+Q243K,Y174L+Q243E, Y174L+R244K, Y174L+R244V, Y174L+A250G, Y174L+K254Y,Y174L+G257W, Y174L+G257E, Y174L+G257A, Y174L+W260F, Y174L+W260Y,Y174L+W260L, Y174L+W260T, Y174L+Y262F, Y174L+S266A, Y174L+D268N,Y174L+A270D, Y174L+N272M, Y174L+N272T, Y174L+N273E, Y174L+N273D,Y174L+A276E, Y174L+A276W, Y174L+A276D, Y174L+N279D, Y174L+N279E,Y174L+T280L, Y174L+N283W, Y174L+N283H, Y174L+Y286W, Y174L+Y286F,Y174L+L288I, Y174L+E290A, Y174L+L294P, Y174L+L294K, Y174L+L294I,Y174L+L294R, Y174L+L294V, Y174L+L294H, Y174L+S295K, Y174L+S295V,Y174L+S295P, Y174L+S295L, Y174L+S295R, Y174L+S295A, Y174L+S295N,Y174L+S295M, Y174L+S295I, Y174L+T296S, Y174L+F298Y, Y174W+R176Q,Y174W+E177S, Y174W+E177Y, Y174W+N180R, Y174W+P183T, Y174W+P183G,Y174W+Q184E, Y174W+Q184K, Y174W+R185G, Y174W+Y196W, Y174W+Y196F,Y174W+N200T, Y174W+S202R, Y174W+Q203T, Y174W+R205K, Y174W+R210L,Y174W+R210G, Y174W+R210M, Y174W+N213V, Y174W+N213D, Y174W+T228S,Y174W+N229D, Y174W+E234F, Y174W+E234Y, Y174W+A235K, Y174W+A235R,Y174W+S241C, Y174W+Q243K, Y174W+Q243E, Y174W+R244K, Y174W+R244V,Y174W+A250G, Y174W+K254Y, Y174W+G257W, Y174W+G257E, Y174W+G257A,Y174W+W260F, Y174W+W260Y, Y174W+W260L, Y174W+W260T, Y174W+Y262F,Y174W+S266A, Y174W+D268N, Y174W+A270D, Y174W+N272M, Y174W+N272T,Y174W+N273E, Y174W+N273D, Y174W+A276E, Y174W+A276W, Y174W+A276D,Y174W+N279D, Y174W+N279E, Y174W+T280L, Y174W+N283W, Y174W+N283H,Y174W+Y286W, Y174W+Y286F, Y174W+L288I, Y174W+E290A, Y174W+L294P,Y174W+L294K, Y174W+L294I, Y174W+L294R, Y174W+L294V, Y174W+L294H,Y174W+S295K, Y174W+S295V, Y174W+S295P, Y174W+S295L, Y174W+S295R,Y174W+S295A, Y174W+S295N, Y174W+S295M, Y174W+S295I, Y174W+T296S,Y174W+F298Y, Y174F+R176Q, Y174F+E177S, Y174F+E177Y, Y174F+N180R,Y174F+P183T, Y174F+P183G, Y174F+Q184E, Y174F+Q184K, Y174F+R185G,Y174F+Y196W, Y174F+Y196F, Y174F+N200T, Y174F+S202R, Y174F+Q203T,Y174F+R205K, Y174F+R210L, Y174F+R210G, Y174F+R210M, Y174F+N213V,Y174F+N213D, Y174F+T228S, Y174F+N229D, Y174F+E234F, Y174F+E234Y,Y174F+A235K, Y174F+A235R, Y174F+S241C, Y174F+Q243K, Y174F+Q243E,Y174F+R244K, Y174F+R244V, Y174F+A250G, Y174F+K254Y, Y174F+G257W,Y174F+G257E, Y174F+G257A, Y174F+W260F, Y174F+W260Y, Y174F+W260L,Y174F+W260T, Y174F+Y262F, Y174F+S266A, Y174F+D268N, Y174F+A270D,Y174F+N272M, Y174F+N272T, Y174F+N273E, Y174F+N273D, Y174F+A276E,Y174F+A276W, Y174F+A276D, Y174F+N279D, Y174F+N279E, Y174F+T280L,Y174F+N283W, Y174F+N283H, Y174F+Y286W, Y174F+Y286F, Y174F+L288I,Y174F+E290A, Y174F+L294P, Y174F+L294K, Y174F+L294I, Y174F+L294R,Y174F+L294V, Y174F+L294H, Y174F+S295K, Y174F+S295V, Y174F+S295P,Y174F+S295L, Y174F+S295R, Y174F+S295A, Y174F+S295N, Y174F+S295M,Y174F+S295I, Y174F+T296S, Y174F+F298Y, R176Q+E177S, R176Q+E177Y,R176Q+N180R, R176Q+P183T, R176Q+P183G, R176Q+Q184E, R176Q+Q184K,R176Q+R185G, R176Q+Y196W, R176Q+Y196F, R176Q+N200T, R176Q+S202R,R176Q+Q203T, R176Q+R205K, R176Q+R210L, R176Q+R210G, R176Q+R210M,R176Q+N213V, R176Q+N213D, R176Q+T228S, R176Q+N229D, R176Q+E234F,R176Q+E234Y, R176Q+A235K, R176Q+A235R, R176Q+S241C, R176Q+Q243K,R176Q+Q243E, R176Q+R244K, R176Q+R244V, R176Q+A250G, R176Q+K254Y,R176Q+G257W, R176Q+G257E, R176Q+G257A, R176Q+W260F, R176Q+W260Y,R176Q+W260L, R176Q+W260T, R176Q+Y262F, R176Q+S266A, R176Q+D268N,R176Q+A270D, R176Q+N272M, R176Q+N272T, R176Q+N273E, R176Q+N273D,R176Q+A276E, R176Q+A276W, R176Q+A276D, R176Q+N279D, R176Q+N279E,R176Q+T280L, R176Q+N283W, R176Q+N283H, R176Q+Y286W, R176Q+Y286F,R176Q+L288I, R176Q+E290A, R176Q+L294P, R176Q+L294K, R176Q+L294I,R176Q+L294R, R176Q+L294V, R176Q+L294H, R176Q+S295K, R176Q+S295V,R176Q+S295P, R176Q+S295L, R176Q+S295R, R176Q+S295A, R176Q+S295N,R176Q+S295M, R176Q+S295I, R176Q+T296S, R176Q+F298Y, E177S+N180R,E177S+P183T, E177S+P183G, E177S+Q184E, E177S+Q184K, E177S+R185G,E177S+Y196W, E177S+Y196F, E177S+N200T, E177S+S202R, E177S+Q203T,E177S+R205K, E177S+R210L, E177S+R210G, E177S+R210M, E177S+N213V,E177S+N213D, E177S+T228S, E177S+N229D, E177S+E234F, E177S+E234Y,E177S+A235K, E177S+A235R, E177S+S241C, E177S+Q243K, E177S+Q243E,E177S+R244K, E177S+R244V, E177S+A250G, E177S+K254Y, E177S+G257W,E177S+G257E, E177S+G257A, E177S+W260F, E177S+W260Y, E177S+W260L,E177S+W260T, E177S+Y262F, E177S+S266A, E177S+D268N, E177S+A270D,E177S+N272M, E177S+N272T, E177S+N273E, E177S+N273D, E177S+A276E,E177S+A276W, E177S+A276D, E177S+N279D, E177S+N279E, E177S+T280L,E177S+N283W, E177S+N283H, E177S+Y286W, E177S+Y286F, E177S+L288I,E177S+E290A, E177S+L294P, E177S+L294K, E177S+L294I, E177S+L294R,E177S+L294V, E177S+L294H, E177S+S295K, E177S+S295V, E177S+S295P,E177S+S295L, E177S+S295R, E177S+S295A, E177S+S295N, E177S+S295M,E177S+S295I, E177S+T296S, E177S+F298Y, E177Y+N180R, E177Y+P183T,E177Y+P183G, E177Y+Q184E, E177Y+Q184K, E177Y+R185G, E177Y+Y196W,E177Y+Y196F, E177Y+N200T, E177Y+S202R, E177Y+Q203T, E177Y+R205K,E177Y+R210L, E177Y+R210G, E177Y+R210M, E177Y+N213V, E177Y+N213D,E177Y+T228S, E177Y+N229D, E177Y+E234F, E177Y+E234Y, E177Y+A235K,E177Y+A235R, E177Y+S241C, E177Y+Q243K, E177Y+Q243E, E177Y+R244K,E177Y+R244V, E177Y+A250G, E177Y+K254Y, E177Y+G257W, E177Y+G257E,E177Y+G257A, E177Y+W260F, E177Y+W260Y, E177Y+W260L, E177Y+W260T,E177Y+Y262F, E177Y+S266A, E177Y+D268N, E177Y+A270D, E177Y+N272M,E177Y+N272T, E177Y+N273E, E177Y+N273D, E177Y+A276E, E177Y+A276W,E177Y+A276D, E177Y+N279D, E177Y+N279E, E177Y+T280L, E177Y+N283W,E177Y+N283H, E177Y+Y286W, E177Y+Y286F, E177Y+L288I, E177Y+E290A,E177Y+L294P, E177Y+L294K, E177Y+L294I, E177Y+L294R, E177Y+L294V,E177Y+L294H, E177Y+S295K, E177Y+S295V, E177Y+S295P, E177Y+S295L,E177Y+S295R, E177Y+S295A, E177Y+S295N, E177Y+S295M, E177Y+S295I,E177Y+T296S, E177Y+F298Y, N180R+P183T, N180R+P183G, N180R+Q184E,N180R+Q184K, N180R+R185G, N180R+Y196W, N180R+Y196F, N180R+N200T,N180R+S202R, N180R+Q203T, N180R+R205K, N180R+R210L, N180R+R210G,N180R+R210M, N180R+N213V, N180R+N213D, N180R+T228S, N180R+N229D,N180R+E234F, N180R+E234Y, N180R+A235K, N180R+A235R, N180R+S241C,N180R+Q243K, N180R+Q243E, N180R+R244K, N180R+R244V, N180R+A250G,N180R+K254Y, N180R+G257W, N180R+G257E, N180R+G257A, N180R+W260F,N180R+W260Y, N180R+W260L, N180R+W260T, N180R+Y262F, N180R+S266A,N180R+D268N, N180R+A270D, N180R+N272M, N180R+N272T, N180R+N273E,N180R+N273D, N180R+A276E, N180R+A276W, N180R+A276D, N180R+N279D,N180R+N279E, N180R+T280L, N180R+N283W, N180R+N283H, N180R+Y286W,N180R+Y286F, N180R+L288I, N180R+E290A, N180R+L294P, N180R+L294K,N180R+L294I, N180R+L294R, N180R+L294V, N180R+L294H, N180R+S295K,N180R+S295V, N180R+S295P, N180R+S295L, N180R+S295R, N180R+S295A,N180R+S295N, N180R+S295M, N180R+S295I, N180R+T296S, N180R+F298Y,P183T+Q184E, P183T+Q184K, P183T+R185G, P183T+Y196W, P183T+Y196F,P183T+N200T, P183T+S202R, P183T+Q203T, P183T+R205K, P183T+R210L,P183T+R210G, P183T+R210M, P183T+N213V, P183T+N213D, P183T+T228S,P183T+N229D, P183T+E234F, P183T+E234Y, P183T+A235K, P183T+A235R,P183T+S241C, P183T+Q243K, P183T+Q243E, P183T+R244K, P183T+R244V,P183T+A250G, P183T+K254Y, P183T+G257W, P183T+G257E, P183T+G257A,P183T+W260F, P183T+W260Y, P183T+W260L, P183T+W260T, P183T+Y262F,P183T+S266A, P183T+D268N, P183T+A270D, P183T+N272M, P183T+N272T,P183T+N273E, P183T+N273D, P183T+A276E, P183T+A276W, P183T+A276D,P183T+N279D, P183T+N279E, P183T+T280L, P183T+N283W, P183T+N283H,P183T+Y286W, P183T+Y286F, P183T+L288I, P183T+E290A, P183T+L294P,P183T+L294K, P183T+L294I, P183T+L294R, P183T+L294V, P183T+L294H,P183T+S295K, P183T+S295V, P183T+S295P, P183T+S295L, P183T+S295R,P183T+S295A, P183T+S295N, P183T+S295M, P183T+S295I, P183T+T296S,P183T+F298Y, P183G+Q184E, P183G+Q184K, P183G+R185G, P183G+Y196W,P183G+Y196F, P183G+N200T, P183G+S202R, P183G+Q203T, P183G+R205K,P183G+R210L, P183G+R210G, P183G+R210M, P183G+N213V, P183G+N213D,P183G+T228S, P183G+N229D, P183G+E234F, P183G+E234Y, P183G+A235K,P183G+A235R, P183G+S241C, P183G+Q243K, P183G+Q243E, P183G+R244K,P183G+R244V, P183G+A250G, P183G+K254Y, P183G+G257W, P183G+G257E,P183G+G257A, P183G+W260F, P183G+W260Y, P183G+W260L, P183G+W260T,P183G+Y262F, P183G+S266A, P183G+D268N, P183G+A270D, P183G+N272M,P183G+N272T, P183G+N273E, P183G+N273D, P183G+A276E, P183G+A276W,P183G+A276D, P183G+N279D, P183G+N279E, P183G+T280L, P183G+N283W,P183G+N283H, P183G+Y286W, P183G+Y286F, P183G+L288I, P183G+E290A,P183G+L294P, P183G+L294K, P183G+L294I, P183G+L294R, P183G+L294V,P183G+L294H, P183G+S295K, P183G+S295V, P183G+S295P, P183G+S295L,P183G+S295R, P183G+S295A, P183G+S295N, P183G+S295M, P183G+S295I,P183G+T296S, P183G+F298Y, Q184E+R185G, Q184E+Y196W, Q184E+Y196F,Q184E+N200T, Q184E+S202R, Q184E+Q203T, Q184E+R205K, Q184E+R210L,Q184E+R210G, Q184E+R210M, Q184E+N213V, Q184E+N213D, Q184E+T228S,Q184E+N229D, Q184E+E234F, Q184E+E234Y, Q184E+A235K, Q184E+A235R,Q184E+S241C, Q184E+Q243K, Q184E+Q243E, Q184E+R244K, Q184E+R244V,Q184E+A250G, Q184E+K254Y, Q184E+G257W, Q184E+G257E, Q184E+G257A,Q184E+W260F, Q184E+W260Y, Q184E+W260L, Q184E+W260T, Q184E+Y262F,Q184E+S266A, Q184E+D268N, Q184E+A270D, Q184E+N272M, Q184E+N272T,Q184E+N273E, Q184E+N273D, Q184E+A276E, Q184E+A276W, Q184E+A276D,Q184E+N279D, Q184E+N279E, Q184E+T280L, Q184E+N283W, Q184E+N283H,Q184E+Y286W, Q184E+Y286F, Q184E+L288I, Q184E+E290A, Q184E+L294P,Q184E+L294K, Q184E+L294I, Q184E+L294R, Q184E+L294V, Q184E+L294H,Q184E+S295K, Q184E+S295V, Q184E+S295P, Q184E+S295L, Q184E+S295R,Q184E+S295A, Q184E+S295N, Q184E+S295M, Q184E+S295I, Q184E+T296S,Q184E+F298Y, Q184K+R185G, Q184K+Y196W, Q184K+Y196F, Q184K+N200T,Q184K+S202R, Q184K+Q203T, Q184K+R205K, Q184K+R210L, Q184K+R210G,Q184K+R210M, Q184K+N213V, Q184K+N213D, Q184K+T228S, Q184K+N229D,Q184K+E234F, Q184K+E234Y, Q184K+A235K, Q184K+A235R, Q184K+S241C,Q184K+Q243K, Q184K+Q243E, Q184K+R244K, Q184K+R244V, Q184K+A250G,Q184K+K254Y, Q184K+G257W, Q184K+G257E, Q184K+G257A, Q184K+W260F,Q184K+W260Y, Q184K+W260L, Q184K+W260T, Q184K+Y262F, Q184K+S266A,Q184K+D268N, Q184K+A270D, Q184K+N272M, Q184K+N272T, Q184K+N273E,Q184K+N273D, Q184K+A276E, Q184K+A276W, Q184K+A276D, Q184K+N279D,Q184K+N279E, Q184K+T280L, Q184K+N283W, Q184K+N283H, Q184K+Y286W,Q184K+Y286F, Q184K+L288I, Q184K+E290A, Q184K+L294P, Q184K+L294K,Q184K+L294I, Q184K+L294R, Q184K+L294V, Q184K+L294H, Q184K+S295K,Q184K+S295V, Q184K+S295P, Q184K+S295L, Q184K+S295R, Q184K+S295A,Q184K+S295N, Q184K+S295M, Q184K+S295I, Q184K+T296S, Q184K+F298Y,R185G+Y196W, R185G+Y196F, R185G+N200T, R185G+S202R, R185G+Q203T,R185G+R205K, R185G+R210L, R185G+R210G, R185G+R210M, R185G+N213V,R185G+N213D, R185G+T228S, R185G+N229D, R185G+E234F, R185G+E234Y,R185G+A235K, R185G+A235R, R185G+S241C, R185G+Q243K, R185G+Q243E,R185G+R244K, R185G+R244V, R185G+A250G, R185G+K254Y, R185G+G257W,R185G+G257E, R185G+G257A, R185G+W260F, R185G+W260Y, R185G+W260L,R185G+W260T, R185G+Y262F, R185G+S266A, R185G+D268N, R185G+A270D,R185G+N272M, R185G+N272T, R185G+N273E, R185G+N273D, R185G+A276E,R185G+A276W, R185G+A276D, R185G+N279D, R185G+N279E, R185G+T280L,R185G+N283W, R185G+N283H, R185G+Y286W, R185G+Y286F, R185G+L288I,R185G+E290A, R185G+L294P, R185G+L294K, R185G+L294I, R185G+L294R,R185G+L294V, R185G+L294H, R185G+S295K, R185G+S295V, R185G+S295P,R185G+S295L, R185G+S295R, R185G+S295A, R185G+S295N, R185G+S295M,R185G+S295I, R185G+T296S, R185G+F298Y, Y196W+N200T, Y196W+S202R,Y196W+Q203T, Y196W+R205K, Y196W+R210L, Y196W+R210G, Y196W+R210M,Y196W+N213V, Y196W+N213D, Y196W+T228S, Y196W+N229D, Y196W+E234F,Y196W+E234Y, Y196W+A235K, Y196W+A235R, Y196W+S241C, Y196W+Q243K,Y196W+Q243E, Y196W+R244K, Y196W+R244V, Y196W+A250G, Y196W+K254Y,Y196W+G257W, Y196W+G257E, Y196W+G257A, Y196W+W260F, Y196W+W260Y,Y196W+W260L, Y196W+W260T, Y196W+Y262F, Y196W+S266A, Y196W+D268N,Y196W+A270D, Y196W+N272M, Y196W+N272T, Y196W+N273E, Y196W+N273D,Y196W+A276E, Y196W+A276W, Y196W+A276D, Y196W+N279D, Y196W+N279E,Y196W+T280L, Y196W+N283W, Y196W+N283H, Y196W+Y286W, Y196W+Y286F,Y196W+L288I, Y196W+E290A, Y196W+L294P, Y196W+L294K, Y196W+L294I,Y196W+L294R, Y196W+L294V, Y196W+L294H, Y196W+S295K, Y196W+S295V,Y196W+S295P, Y196W+S295L, Y196W+S295R, Y196W+S295A, Y196W+S295N,Y196W+S295M, Y196W+S295I, Y196W+T296S, Y196W+F298Y, Y196F+N200T,Y196F+S202R, Y196F+Q203T, Y196F+R205K, Y196F+R210L, Y196F+R210G,Y196F+R210M, Y196F+N213V, Y196F+N213D, Y196F+T228S, Y196F+N229D,Y196F+E234F, Y196F+E234Y, Y196F+A235K, Y196F+A235R, Y196F+S241C,Y196F+Q243K, Y196F+Q243E, Y196F+R244K, Y196F+R244V, Y196F+A250G,Y196F+K254Y, Y196F+G257W, Y196F+G257E, Y196F+G257A, Y196F+W260F,Y196F+W260Y, Y196F+W260L, Y196F+W260T, Y196F+Y262F, Y196F+S266A,Y196F+D268N, Y196F+A270D, Y196F+N272M, Y196F+N272T, Y196F+N273E,Y196F+N273D, Y196F+A276E, Y196F+A276W, Y196F+A276D, Y196F+N279D,Y196F+N279E, Y196F+T280L, Y196F+N283W, Y196F+N283H, Y196F+Y286W,Y196F+Y286F, Y196F+L288I, Y196F+E290A, Y196F+L294P, Y196F+L294K,Y196F+L294I, Y196F+L294R, Y196F+L294V, Y196F+L294H, Y196F+S295K,Y196F+S295V, Y196F+S295P, Y196F+S295L, Y196F+S295R, Y196F+S295A,Y196F+S295N, Y196F+S295M, Y196F+S295I, Y196F+T296S, Y196F+F298Y,N200T+S202R, N200T+Q203T, N200T+R205K, N200T+R210L, N200T+R210G,N200T+R210M, N200T+N213V, N200T+N213D, N200T+T228S, N200T+N229D,N200T+E234F, N200T+E234Y, N200T+A235K, N200T+A235R, N200T+S241C,N200T+Q243K, N200T+Q243E, N200T+R244K, N200T+R244V, N200T+A250G,N200T+K254Y, N200T+G257W, N200T+G257E, N200T+G257A, N200T+W260F,N200T+W260Y, N200T+W260L, N200T+W260T, N200T+Y262F, N200T+S266A,N200T+D268N, N200T+A270D, N200T+N272M, N200T+N272T, N200T+N273E,N200T+N273D, N200T+A276E, N200T+A276W, N200T+A276D, N200T+N279D,N200T+N279E, N200T+T280L, N200T+N283W, N200T+N283H, N200T+Y286W,N200T+Y286F, N200T+L288I, N200T+E290A, N200T+L294P, N200T+L294K,N200T+L294I, N200T+L294R, N200T+L294V, N200T+L294H, N200T+S295K,N200T+S295V, N200T+S295P, N200T+S295L, N200T+S295R, N200T+S295A,N200T+S295N, N200T+S295M, N200T+S295I, N200T+T296S, N200T+F298Y,S202R+Q203T, S202R+R205K, S202R+R210L, S202R+R210G, S202R+R210M,S202R+N213V, S202R+N213D, S202R+T228S, S202R+N229D, S202R+E234F,S202R+E234Y, S202R+A235K, S202R+A235R, S202R+S2410, S202 R+Q243 K, S202R+Q243 E, S202R+R244K, S202R+R244V, S202R+A250G, S202R+K254Y,S202R+G257W, S202R+G257E, S202R+G257A, S202R+W260F, S202R+W260Y, S202R+W260L, S202R+W260T, S202R+Y262F, S202R+S266A, S202R+D268N,S202R+A270D, S202R+N272M, S202R+N272T, S202R+N273E, S202R+N273D,S202R+A276E, S202R+A276W, S202R+A276D, S202R+N279D, S202R+N279E,S202R+T280L, S202R+N283W, S202R+N283H, S202R+Y286W, S202R+Y286F,S202R+L288I, S202R+E290A, S202R+L294P, S202R+L294K, S202R+L294I,S202R+L294R, S202R+L294V, S202R+L294H, S202R+S295K, S202R+S295V,S202R+S295P, S202R+S295L, S202R+S295R, S202R+S295A, S202R+S295N,S202R+S295M, S202R+S295I, S202R+T296S, S202R+F298Y, Q203T+R205K,Q203T+R210L, Q203T+R210G, Q203T+R210M, Q203T+N213V, Q203T+N213D,Q203T+T228S, Q203T+N229D, Q203T+E234F, Q203T+E234Y, Q203T+A235K,Q203T+A235R, Q203T+S2410, Q203T+Q243K, Q203T+Q243E, Q203T+R244K,Q203T+R244V, Q203T+A250G, Q203T+K254Y, Q203T+G257W, Q203T+G257E,Q203T+G257A, Q203T+W260F, Q203T+W260Y, Q203T+W260L, Q203T+W260T,Q203T+Y262F, Q203T+S266A, Q203T+D268N, Q203T+A270D, Q203T+N272M,Q203T+N272T, Q203T+N273E, Q203T+N273D, Q203T+A276E, Q203T+A276W,Q203T+A276D, Q203T+N279D, Q203T+N279E, Q203T+T280L, Q203T+N283W,Q203T+N283H, Q203T+Y286W, Q203T+Y286F, Q203T+L288I, Q203T+E290A,Q203T+L294P, Q203T+L294K, Q203T+L294I, Q203T+L294R, Q203T+L294V,Q203T+L294H, Q203T+S295K, Q203T+S295V, Q203T+S295P, Q203T+S295L,Q203T+S295R, Q203T+S295A, Q203T+S295N, Q203T+S295M, Q203T+S295I,Q203T+T296S, Q203T+F298Y, R205K+R210L, R205K+R210G, R205K+R210M,R205K+N213V, R205K+N213D, R205K+T228S, R205K+N229D, R205K+E234F,R205K+E234Y, R205K+A235K, R205K+A235R, R205K+S241C, R205K+Q243K,R205K+Q243E, R205K+R244K, R205K+R244V, R205K+A250G, R205K+K254Y,R205K+G257W, R205K+G257E, R205K+G257A, R205K+W260F, R205K+W260Y,R205K+W260L, R205K+W260T, R205K+Y262F, R205K+S266A, R205K+D268N,R205K+A270D, R205K+N272M, R205K+N272T, R205K+N273E, R205K+N273D,R205K+A276E, R205K+A276W, R205K+A276D, R205K+N279D, R205K+N279E,R205K+T280L, R205K+N283W, R205K+N283H, R205K+Y286W, R205K+Y286F,R205K+L288I, R205K+E290A, R205K+L294P, R205K+L294K, R205K+L294I,R205K+L294R, R205K+L294V, R205K+L294H, R205K+S295K, R205K+S295V,R205K+S295P, R205K+S295L, R205K+S295R, R205K+S295A, R205K+S295N,R205K+S295M, R205K+S295I, R205K+T296S, R205K+F298Y, R210L+N213V,R210L+N213D, R210L+T228S, R210L+N229D, R210L+E234F, R210L+E234Y,R210L+A235K, R210L+A235R, R210L+S241C, R210L+Q243K, R210L+Q243E,R210L+R244K, R210L+R244V, R210L+A250G, R210L+K254Y, R210L+G257W,R210L+G257E, R210L+G257A, R210L+W260F, R210L+W260Y, R210L+W260 L,R210L+W260T, R210L+Y262F, R210L+S266A, R210L+D268N, R210L+A270D,R210L+N272M, R210L+N272T, R210L+N273E, R210L+N273D, R210L+A276E,R210L+A276W, R210L+A276D, R210L+N279D, R210L+N279E, R210L+T280L,R210L+N283W, R210L+N283H, R210L+Y286W, R210L+Y286F, R210L+L288I,R210L+E290A, R210L+L294P, R210L+L294K, R210L+L294I, R210L+L294R,R210L+L294V, R210L+L294H, R210L+S295K, R210L+S295V, R210L+S295P,R210L+S295L, R210L+S295R, R210L+S295A, R210L+S295N, R210L+S295M,R210L+S295I, R210L+T296S, R210L+F298Y, R210G+N213V, R210G+N213D,R210G+T228S, R210G+N229D, R210G+E234F, R210G+E234Y, R210G+A235K,R210G+A235R, R210G+S241C, R210G+Q243K, R210G+Q243E, R210G+R244K,R210G+R244V, R210G+A250G, R210G+K254Y, R210G+G257W, R210G+G257E,R210G+G257A, R210G+W260F, R210G+W260Y, R210G+W260L, R210G+W260T,R210G+Y262F, R210G+S266A, R210G+D268N, R210G+A270D, R210G+N272M,R210G+N272T, R210G+N273E, R210G+N273D, R210G+A276E, R210G+A276W,R210G+A276D, R210G+N279D, R210G+N279E, R210G+T280L, R210G+N283W,R210G+N283H, R210G+Y286W, R210G+Y286F, R210G+L288I, R210G+E290A,R210G+L294P, R210G+L294K, R210G+L294I, R210G+L294R, R210G+L294V,R210G+L294H, R210G+S295K, R210G+S295V, R210G+S295P, R210G+S295L,R210G+S295R, R210G+S295A, R210G+S295N, R210G+S295M, R210G+S295I,R210G+T296S, R210G+F298Y, R210M+N213V, R210M+N213D, R210M+T228S,R210M+N229D, R210M+E234F, R210M+E234Y, R210M+A235K, R210M+A235R,R210M+S241C, R210M+Q243K, R210M+Q243E, R210M+R244K, R210M+R244V,R210M+A250G, R210M+K254Y, R210M+G257W, R210M+G257E, R210M+G257A,R210M+W260F, R210M+W260Y, R210M+W260L, R210M+W260T, R210M+Y262F,R210M+S266A, R210M+D268N, R210M+A270D, R210M+N272M, R210M+N272T,R210M+N273E, R210M+N273D, R210M+A276E, R210M+A276W, R210M+A276D,R210M+N279D, R210M+N279E, R210M+T280L, R210M+N283W, R210M+N283H,R210M+Y286W, R210M+Y286F, R210M+L288I, R210M+E290A, R210M+L294P,R210M+L294K, R210M+L294I, R210M+L294R, R210M+L294V, R210M+L294H,R210M+S295K, R210M+S295V, R210M+S295P, R210M+S295L, R210M+S295R,R210M+S295A, R210M+S295N, R210M+S295M, R210M+S295I, R210M+T296S,R210M+F298Y, N213V+T228S, N213V+N229D, N213V+E234F, N213V+E234Y,N213V+A235K, N213V+A235R, N213V+S241C, N213V+Q243K, N213V+Q243E,N213V+R244K, N213V+R244V, N213V+A250G, N213V+K254Y, N213V+G257W,N213V+G257E, N213V+G257A, N213V+W260F, N213V+W260Y, N213V+W260L,N213V+W260T, N213V+Y262F, N213V+S266A, N213V+D268N, N213V+A270D,N213V+N272M, N213V+N272T, N213V+N273E, N213V+N273D, N213V+A276E,N213V+A276W, N213V+A276D, N213V+N279D, N213V+N279E, N213V+T280L,N213V+N283W, N213V+N283H, N213V+Y286W, N213V+Y286F, N213V+L288I,N213V+E290A, N213V+L294P, N213V+L294K, N213V+L294I, N213V+L294R,N213V+L294V, N213V+L294H, N213V+S295K, N213V+S295V, N213V+S295P,N213V+S295L, N213V+S295R, N213V+S295A, N213V+S295N, N213V+S295M,N213V+S295I, N213V+T296S, N213V+F298Y, N213D+T228S, N213D+N229D,N213D+E234F, N213D+E234Y, N213D+A235K, N213D+A235R, N213D+S241C,N213D+Q243K, N213D+Q243E, N213D+R244K, N213D+R244V, N213D+A250G,N213D+K254Y, N213D+G257W, N213D+G257E, N213D+G257A, N213D+W260F,N213D+W260Y, N213D+W260L, N213D+W260T, N213D+Y262F, N213D+S266A,N213D+D268N, N213D+A270D, N213D+N272M, N213D+N272T, N213D+N273E,N213D+N273D, N213D+A276E, N213D+A276W, N213D+A276D, N213D+N279D,N213D+N279E, N213D+T280L, N213D+N283W, N213D+N283H, N213D+Y286W,N213D+Y286F, N213D+L288I, N213D+E290A, N213D+L294P, N213D+L294K,N213D+L294I, N213D+L294R, N213D+L294V, N213D+L294H, N213D+S295K,N213D+S295V, N213D+S295P, N213D+S295L, N213D+S295R, N213D+S295A,N213D+S295N, N213D+S295M, N213D+S295I, N213D+T296S, N213D+F298Y,T228S+N229D, T228S+E234F, T228S+E234Y, T228S+A235K, T228S+A235R,T228S+S241C, T228S+Q243K, T228S+Q243E, T228S+R244K, T228S+R244V,T228S+A250G, T228S+K254Y, T228S+G257W, T228S+G257E, T228S+G257A,T228S+W260F, T228S+W260Y, T228S+W260L, T228S+W260T, T228S+Y262F,T228S+S266A, T228S+D268N, T228S+A270D, T228S+N272M, T228S+N272T,T228S+N273E, T228S+N273D, T228S+A276E, T228S+A276W, T228S+A276D,T228S+N279D, T228S+N279E, T228S+T280L, T228S+N283W, T228S+N283H,T228S+Y286W, T228S+Y286F, T228S+L288I, T228S+E290A, T228S+L294P,T228S+L294K, T228S+L294I, T228S+L294R, T228S+L294V, T228S+L294H,T228S+S295K, T228S+S295V, T228S+S295P, T228S+S295L, T228S+S295R,T228S+S295A, T228S+S295N, T228S+S295M, T228S+S295I, T228S+T296S,T228S+F298Y, N229D+E234F, N229D+E234Y, N229D+A235K, N229D+A235R,N229D+S241C, N229D+Q243K, N229D+Q243E, N229D+R244K, N229D+R244V,N229D+A250G, N229D+K254Y, N229D+G257W, N229D+G257E, N229D+G257A,N229D+W260F, N229D+W260Y, N229D+W260L, N229D+W260T, N229D+Y262F,N229D+S266A, N229D+D268N, N229D+A270D, N229D+N272M, N229D+N272T,N229D+N273E, N229D+N273D, N229D+A276E, N229D+A276W, N229D+A276D,N229D+N279D, N229D+N279E, N229D+T280L, N229D+N283W, N229D+N283H,N229D+Y286W, N229D+Y286F, N229D+L288I, N229D+E290A, N229D+L294P,N229D+L294K, N229D+L294I, N229D+L294R, N229D+L294V, N229D+L294H,N229D+S295K, N229D+S295V, N229D+S295P, N229D+S295L, N229D+S295R,N229D+S295A, N229D+S295N, N229D+S295M, N229D+S295I, N229D+T296S,N229D+F298Y, E234F+A235K, E234F+A235R, E234F+S241C, E234F+Q243K,E234F+Q243E, E234F+R244K, E234F+R244V, E234F+A250G, E234F+K254Y,E234F+G257W, E234F+G257E, E234F+G257A, E234F+W260F, E234F+W260Y,E234F+W260L, E234F+W260T, E234F+Y262F, E234F+S266A, E234F+D268N,E234F+A270D, E234F+N272M, E234F+N272T, E234F+N273E, E234F+N273D,E234F+A276E, E234F+A276W, E234F+A276D, E234F+N279D, E234F+N279E,E234F+T280L, E234F+N283W, E234F+N283H, E234F+Y286W, E234F+Y286F,E234F+L288I, E234F+E290A, E234F+L294P, E234F+L294K, E234F+L294I,E234F+L294R, E234F+L294V, E234F+L294H, E234F+S295K, E234F+S295V,E234F+S295P, E234F+S295L, E234F+S295R, E234F+S295A, E234F+S295N,E234F+S295M, E234F+S295I, E234F+T296S, E234F+F298Y, E234Y+A235K,E234Y+A235R, E234Y+S241C, E234Y+Q243K, E234Y+Q243E, E234Y+R244K,E234Y+R244V, E234Y+A250G, E234Y+K254Y, E234Y+G257W, E234Y+G257E,E234Y+G257A, E234Y+W260F, E234Y+W260Y, E234Y+W260L, E234Y+W260T,E234Y+Y262F, E234Y+S266A, E234Y+D268N, E234Y+A270D, E234Y+N272M,E234Y+N272T, E234Y+N273E, E234Y+N273D, E234Y+A276E, E234Y+A276W,E234Y+A276D, E234Y+N279D, E234Y+N279E, E234Y+T280L, E234Y+N283W,E234Y+N283H, E234Y+Y286W, E234Y+Y286F, E234Y+L288I, E234Y+E290A,E234Y+L294P, E234Y+L294K, E234Y+L294I, E234Y+L294R, E234Y+L294V,E234Y+L294H, E234Y+S295K, E234Y+S295V, E234Y+S295P, E234Y+S295L,E234Y+S295R, E234Y+S295A, E234Y+S295N, E234Y+S295M, E234Y+S295I,E234Y+T296S, E234Y+F298Y, A235K+S241C, A235K+Q243K, A235K+Q243E,A235K+R244K, A235K+R244V, A235K+A250G, A235K+K254Y, A235K+G257W,A235K+G257E, A235K+G257A, A235K+W260F, A235K+W260Y, A235K+W260L,A235K+W260T, A235K+Y262F, A235K+S266A, A235K+D268N, A235K+A270D,A235K+N272M, A235K+N272T, A235K+N273E, A235K+N273D, A235K+A276E,A235K+A276W, A235K+A276D, A235K+N279D, A235K+N279E, A235K+T280L,A235K+N283W, A235K+N283H, A235K+Y286W, A235K+Y286F, A235K+L288I,A235K+E290A, A235K+L294P, A235K+L294K, A235K+L294I, A235K+L294R,A235K+L294V, A235K+L294H, A235K+S295K, A235K+S295V, A235K+S295P,A235K+S295L, A235K+S295R, A235K+S295A, A235K+S295N, A235K+S295M,A235K+S295I, A235K+T296S, A235K+F298Y, A235R+S241C, A235R+Q243K,A235R+Q243E, A235R+R244K, A235R+R244V, A235R+A250G, A235R+K254Y,A235R+G257W, A235R+G257E, A235R+G257A, A235R+W260F, A235R+W260Y,A235R+W260L, A235R+W260T, A235R+Y262F, A235R+S266A, A235R+D268N,A235R+A270D, A235R+N272M, A235R+N272T, A235R+N273E, A235R+N273D,A235R+A276E, A235R+A276W, A235R+A276D, A235R+N279D, A235R+N279E,A235R+T280L, A235R+N283W, A235R+N283H, A235R+Y286W, A235R+Y286F,A235R+L288I, A235R+E290A, A235R+L294P, A235R+L294K, A235R+L294I,A235R+L294R, A235R+L294V, A235R+L294 H, A235R+S295K, A235R+S295V,A235R+S295P, A235R+S295L, A235R+S295R, A235R+S295A, A235R+S295N,A235R+S295M, A235R+S295I, A235R+T296S, A235R+F298Y, S241C+Q243K,S241C+Q243E, S241C+R244 K, S241C+R244V, S241C+A250G, S241C+K254Y,S241C+G257W, S241C+G257E, S241C+G257A, S241C+W260F, S241C+W260Y,S241C+W260L, S241C+W260T, S241C+Y262F, S241C+S266A, S241C+D268N,S241C+A270D, S241C+N272M, S241C+N272T, S241C+N273E, S241C+N273D,S241C+A276E, S241C+A276W, S241C+A276D, S241C+N279D, S241C+N279E,S241C+T280L, S241C+N283W, S241C+N283H, S241C+Y286W, S241C+Y286F,S241C+L288I, S241C+E290A, S241C+L294P, S241C+L294K, S241C+L294I,S241C+L294R, S241C+L294V, S241C+L294H, S241C+S295K, S241C+S295V,S241C+S295P, S241C+S295L, S241C+S295R, S241C+S295A, S241C+S295N,S241C+S295M, S241C+S295I, S241C+T296S, S241C+F298Y, Q243K+R244K,Q243K+R244V, Q243 K+A250G, Q243K+K254Y, Q243K+G257W, Q243K+G257E,Q243K+G257A, Q243K+W260F, Q243K+W260Y, Q243K+W260L, Q243 K+W260T,Q243K+Y262F, Q243K+S266A, Q243K+D268N, Q243K+A270D, Q243 K+N272M,Q243K+N272T, Q243 K+N273E, Q243K+N273D, Q243 K+A276 E, Q243K+A276W,Q243K+A276D, Q243 K+N279D, Q243K+N279 E, Q243K+T280L, Q243K+N283W, Q243K+N283H, Q243K+Y286W, Q243K+Y286F, Q243K+L288I, Q243K+E290A,Q243K+L294P, Q243K+L294K, Q243K+L294I, Q243K+L294 R, Q243K+L294V,Q243K+L294H, Q243K+S295K, Q243 K+S295V, Q243K+S295P, Q243K+S295L,Q243K+S295R, Q243 K+S295A, Q243 K+S295N, Q243K+S295M, Q243K+S295I,Q243K+T296S, Q243K+F298Y, Q243E+R244K, Q243E+R244V, Q243E+A250G, Q243E+K254Y, Q243E+G257W, Q243 E+G257 E, Q243E+G257A, Q243E+W260F,Q243E+W260Y, Q243E+W260L, Q243 E+W260T, Q243E+Y262F, Q243E+S266A,Q243E+D268N, Q243E+A270D, Q243E+N272M, Q243E+N272T, Q243E+N273E,Q243E+N273D, Q243E+A276E, Q243E+A276W, Q243E+A276D, Q243E+N279D,Q243E+N279E, Q243E+T280L, Q243E+N283W, Q243E+N283H, Q243E+Y286W,Q243E+Y286F, Q243E+L288I, Q243E+E290A, Q243E+L294P, Q243E+L294K,Q243E+L294I, Q243E+L294R, Q243E+L294V, Q243E+L294H, Q243E+S295K,Q243E+S295V, Q243E+S295P, Q243E+S295L, Q243E+S295R, Q243E+S295A,Q243E+S295N, Q243E+S295M, Q243E+S295I, Q243E+T296S, Q243E+F298Y,R244K+A250G, R244K+K254Y, R244 K+G257W, R244K+G257E, R244 K+G257A,R244K+W260F, R244K+W260Y, R244K+W260L, R244K+W260T, R244 K+Y262 F,R244K+S266A, R244K+D268N, R244 K+A270D, R244K+N272M, R244 K+N272T,R244K+N273 E, R244K+N273D, R244K+A276E, R244K+A276W, R244 K+A276D,R244K+N279D, R244K+N279 E, R244K+T280L, R244K+N283W, R244K+N283H,R244K+Y286W, R244K+Y286F, R244K+L288I, R244K+E290A, R244K+L294P, R244K+L294 K, R244K+L294I, R244K+L294R, R244 K+L294V, R244K+L294H,R244K+S295K, R244K+S295V, R244K+S295P, R244K+S295L, R244K+S295R,R244K+S295A, R244K+S295N, R244K+S295M, R244K+S295I, R244K+T296S,R244K+F298Y, R244V+A250G, R244V+K254Y, R244V+G257W, R244V+G257E,R244V+G257A, R244V+W260F, R244V+W260Y, R244V+W260L, R244V+W260T,R244V+Y262F, R244V+S266A, R244V+D268N, R244V+A270D, R244V+N272M,R244V+N272T, R244V+N273E, R244V+N273D, R244V+A276E, R244V+A276W,R244V+A276D, R244V+N279D, R244V+N279E, R244V+T280L, R244V+N283W,R244V+N283H, R244V+Y286W, R244V+Y286F, R244V+L288I, R244V+E290A,R244V+L294P, R244V+L294K, R244V+L294I, R244V+L294R, R244V+L294V,R244V+L294H, R244V+S295K, R244V+S295V, R244V+S295P, R244V+S295L,R244V+S295R, R244V+S295A, R244V+S295N, R244V+S295M, R244V+S295I,R244V+T296S, R244V+F298Y, A250G+K254Y, A250G+G257W, A250G+G257E,A250G+G257A, A250G+W260F, A250G+W260Y, A250G+W260L, A250G+W260T,A250G+Y262F, A250G+S266A, A250G+D268N, A250G+A270D, A250G+N272M,A250G+N272T, A250G+N273E, A250G+N273D, A250G+A276E, A250G+A276W,A250G+A276D, A250G+N279D, A250G+N279E, A250G+T280L, A250G+N283W,A250G+N283H, A250G+Y286W, A250G+Y286F, A250G+L288I, A250G+E290A,A250G+L294P, A250G+L294K, A250G+L294I, A250G+L294R, A250G+L294V,A250G+L294H, A250G+S295K, A250G+S295V, A250G+S295P, A250G+S295L,A250G+S295R, A250G+S295A, A250G+S295N, A250G+S295M, A250G+S295I,A250G+T296S, A250G+F298Y, K254Y+G257W, K254Y+G257E, K254Y+G257A,K254Y+W260F, A250G+W260Y, A250G+W260L, A250G+W260T, K254Y+Y262F,K254Y+S266A, K254Y+D268N, K254Y+A270D, K254Y+N272M, K254Y+N272T,K254Y+N273E, K254Y+N273D, K254Y+A276E, K254Y+A276W, K254Y+A276D,K254Y+N279D, K254Y+N279E, K254Y+T280L, K254Y+N283W, K254Y+N283H,K254Y+Y286W, K254Y+Y286F, K254Y+L288I, K254Y+E290A, K254Y+L294P,K254Y+L294K, K254Y+L294I, K254Y+L294R, K254Y+L294V, K254Y+L294H,K254Y+S295K, K254Y+S295V, K254Y+S295P, K254Y+S295L, K254Y+S295R,K254Y+S295A, K254Y+S295N, K254Y+S295M, K254Y+S295I, K254Y+T296S,K254Y+F298Y, G257W+W260F, G257W+W260Y, G257W+W260L, G257W+W260T,G257W+Y262F, G257W+S266A, G257W+D268N, G257W+A270D, G257W+N272M,G257W+N272T, G257W+N273E, G257W+N273D, G257W+A276E, G257W+A276W,G257W+A276D, G257W+N279D, G257W+N279E, G257W+T280L, G257W+N283W,G257W+N283H, G257W+Y286W, G257W+Y286F, G257W+L288I, G257W+E290A,G257W+L294P, G257W+L294K, G257W+L294I, G257W+L294R, G257W+L294V,G257W+L294H, G257W+S295K, G257W+S295V, G257W+S295P, G257W+S295L,G257W+S295R, G257W+S295A, G257W+S295N, G257W+S295M, G257W+S295I,G257W+T296S, G257W+F298Y, G257E+W260F, G257E+W260Y, G257E+W260L,G257E+W260T, G257E+Y262F, G257E+S266A, G257E+D268N, G257E+A270D,G257E+N272M, G257E+N272T, G257E+N273E, G257E+N273D, G257E+A276E,G257E+A276W, G257E+A276D, G257E+N279D, G257E+N279E, G257E+T280L,G257E+N283W, G257E+N283H, G257E+Y286W, G257E+Y286F, G257E+L288I,G257E+E290A, G257E+L294P, G257E+L294K, G257E+L294I, G257E+L294R,G257E+L294V, G257E+L294H, G257E+S295K, G257E+S295V, G257E+S295P,G257E+S295L, G257E+S295R, G257E+S295A, G257E+S295N, G257E+S295M,G257E+S295I, G257E+T296S, G257E+F298Y, G257A+W260F, G257A+W260Y,G257A+W260L, G257A+W260T, G257A+Y262F, G257A+S266A, G257A+D268N,G257A+A270D, G257A+N272M, G257A+N272T, G257A+N273E, G257A+N273D,G257A+A276E, G257A+A276W, G257A+A276D, G257A+N279D, G257A+N279E,G257A+T280L, G257A+N283W, G257A+N283H, G257A+Y286W, G257A+Y286F,G257A+L288I, G257A+E290A, G257A+L294P, G257A+L294K, G257A+L294I,G257A+L294R, G257A+L294V, G257A+L294H, G257A+S295K, G257A+S295V,G257A+S295P, G257A+S295L, G257A+S295R, G257A+S295A, G257A+S295N,G257A+S295M, G257A+S295I, G257A+T296S, G257A+F298Y, W260F+Y262F,W260F+S266A, W260F+D268N, W260F+A270D, W260F+N272M, W260F+N272T,W260F+N273E, W260F+N273D, W260F+A276E, W260F+A276W, W260F+A276D,W260F+N279D, W260F+N279E, W260F+T280L, W260F+N283W, W260F+N283H,W260F+Y286W, W260F+Y286F, W260F+L288I, W260F+E290A, W260F+L294P,W260F+L294K, W260F+L294I, W260F+L294R, W260F+L294V, W260F+L294H,W260F+S295K, W260F+S295V, W260F+S295P, W260F+S295L, W260F+S295R,W260F+S295A, W260F+S295N, W260F+S295M, W260F+S295I, W260F+T296S,W260F+F298Y, W260Y+Y262F, W260L+Y262F, W260T+Y262F, Y262F+S266A,Y262F+D268N, Y262F+A270D, Y262F+N272M, Y262F+N272T, Y262F+N273E,Y262F+N273D, Y262F+A276E, Y262F+A276W, Y262F+A276D, Y262F+N279D,Y262F+N279E, Y262F+T280L, Y262F+N283W, Y262F+N283H, Y262F+Y286W,Y262F+Y286F, Y262F+L288I, Y262F+E290A, Y262F+L294P, Y262F+L294K,Y262F+L294I, Y262F+L294R, Y262F+L294V, Y262F+L294H, Y262F+S295K,Y262F+S295V, Y262F+S295P, Y262F+S295L, Y262F+S295R, Y262F+S295A,Y262F+S295N, Y262F+S295M, Y262F+S295I, Y262F+T296S, Y262F+F298Y,W260Y+S266A, W260L+S266A, W260T+S266A, S266A+D268N, S266A+A270D,S266A+N272M, S266A+N272T, S266A+N273E, S266A+N273D, S266A+A276E,S266A+A276W, S266A+A276D, S266A+N279D, S266A+N279E, S266A+T280L,S266A+N283W, S266A+N283H, S266A+Y286W, S266A+Y286F, S266A+L288I,S266A+E290A, S266A+L294P, S266A+L294K, S266A+L294I, S266A+L294R,S266A+L294V, S266A+L294H, S266A+S295K, S266A+S295V, S266A+S295P,S266A+S295L, S266A+S295R, S266A+S295A, S266A+S295N, S266A+S295M,S266A+S295I, S266A+T296S, S266A+F298Y, W260Y+D268N, W260 L+D268N,W260T+D268N, D268N+A270D, D268N+N272M, D268 N +N272T, D268N+N273E,D268N+N273D, D268N+A276E, D268N+A276W, D268N+A276D, D268N+N279D,D268N+N279E, D268N+T280L, D268N+N283W, D268N+N283H, D268N+Y286W,D268N+Y286F, D268N+L288I, D268N+E290A, D268N+L294P, D268N+L294K,D268N+L294I, D268N+L294R, D268N+L294V, D268N+L294H, D268N+S295K,D268N+S295V, D268N+S295P, D268N+S295L, D268N+S295R, D268N+S295A,D268N+S295N, D268N+S295M, D268N+S295I, D268N+T296S, D268N+F298Y,W260Y+A270D, W260L+A270D, W260T+A270D, A270D+N272M, A270D+N272T,A270D+N273E, A270D+N273D, A270D+A276E, A270D+A276W, A270D+A276D,A270D+N279D, A270D+N279E, A270D+T280L, A270D+N283W, A270D+N283H,A270D+Y286W, A270D+Y286F, A270D+L288I, A270D+E290A, A270D+L294P,A270D+L294K, A270D+L294I, A270D+L294R, A270D+L294V, A270D+L294H,A270D+S295K, A270D+S295V, A270D+S295P, A270D+S295L, A270D+S295R,A270D+S295A, A270D+S295N, A270D+S295M, A270D+S295I, A270D+T296S,A270D+F298Y, W260Y+N272M, W260L+N272M, W260T+N272M, N272M+N273E,N272M+N273D, N272M+A276E, N272M+A276W, N272M+A276D, N272M+N279D,N272M+N279E, N272M+T280L, N272M+N283W, N272M+N283H, N272M+Y286W,N272M+Y286F, N272M+L288I, N272M+E290A, N272M+L294P, N272M+L294K,N272M+L294I, N272M+L294R, N272M+L294V, N272M+L294H, N272M+S295K,N272M+S295V, N272M+S295P, N272M+S295L, N272M+S295R, N272M+S295A,N272M+S295N, N272M+S295M, N272M+S295I, N272M+T296S, N272M+F298Y,W260Y+N272T, W260L+N272T, W260T+N272T, N272T+N273E, N272T+N273D,N272T+A276E, N272T+A276W, N272T+A276D, N272T+N279D, N272T+N279E,N272T+T280L, N272T+N283W, N272T+N283H, N272T+Y286W, N272T+Y286F,N272T+L288I, N272T+E290A, N272T+L294P, N272T+L294K, N272T+L294I,N272T+L294R, N272T+L294V, N272T+L294H, N272T+S295K, N272T+S295V,N272T+S295P, N272T+S295L, N272T+S295R, N272T+S295A, N272T+S295N,N272T+S295M, N272T+S295I, N272T+T296S, N272T+F298Y, W260Y+N273E,W260L+N273E, W260T+N273E, N273E+A276E, N273E+A276W, N273E+A276D,N273E+N279D, N273E+N279E, N273E+T280L, N273E+N283W, N273E+N283H,N273E+Y286W, N273E+Y286F, N273E+L288I, N273E+E290A, N273E+L294P,N273E+L294K, N273E+L294I, N273E+L294R, N273E+L294V, N273E+L294H,N273E+S295K, N273E+S295V, N273E+S295P, N273E+S295L, N273E+S295R,N273E+S295A, N273E+S295N, N273E+S295M, N273E+S295I, N273E+T296S,N273E+F298Y, W260Y+N273D, W260L+N273D, W260T+N273D, N273D+A276E,N273D+A276W, N273D+A276D, N273D+N279D, N273D+N279E, N273D+T280L,N273D+N283W, N273D+N283H, N273D+Y286W, N273D+Y286F, N273D+L288I,N273D+E290A, N273D+L294P, N273D+L294K, N273D+L294I, N273D+L294R,N273D+L294V, N273D+L294H, N273D+S295K, N273D+S295V, N273D+S295P,N273D+S295L, N273D+S295R, N273D+S295A, N273D+S295N, N273D+S295M,N273D+S295I, N273D+T296S, N273D+F298Y, W260Y+A276E, W260L+A276E,W260T+A276E, A276E+N279D, A276E+N279E, A276E+T280L, A276E+N283W,A276E+N283H, A276E+Y286W, A276E+Y286F, A276E+L288I, A276E+E290A,A276E+L294P, A276E+L294K, A276E+L294I, A276E+L294R, A276E+L294V,A276E+L294H, A276E+S295K, A276E+S295V, A276E+S295P, A276E+S295L,A276E+S295R, A276E+S295A, A276E+S295N, A276E+S295M, A276E+S295I,A276E+T296S, W260Y+A276W, W260L+A276W, W260T+A276W, A276E+F298Y,A276W+N279D, A276W+N279E, A276W+T280L, A276W+N283W, A276W+N283H,A276W+Y286W, A276W+Y286F, A276W+L288I, A276W+E290A, A276W+L294P,A276W+L294K, A276W+L294I, A276W+L294R, A276W+L294V, A276W+L294H,A276W+S295K, A276W+S295V, A276W+S295P, A276W+S295L, A276W+S295R,A276W+S295A, A276W+S295N, A276W+S295M, A276W+S295I, A276W+T296S,A276W+F298Y, W260Y+A276D, W260L+A276D, W260T+A276D, A276D+N279D,A276D+N279E, A276D+T280L, A276D+N283W, A276D+N283H, A276D+Y286W,A276D+Y286F, A276D+L288I, A276D+E290A, A276D+L294P, A276D+L294K,A276D+L294I, A276D+L294R, A276D+L294V, A276D+L294H, A276D+S295K,A276D+S295V, A276D+S295P, A276D+S295L, A276D+S295R, A276D+S295A,A276D+S295N, A276D+S295M, A276D+S295I, A276D+T296S, A276D+F298Y,W260Y+N279D, W260L+N279D, W260T+N279D, N279D+T280L, N279D+N283W,N279D+N283H, N279D+Y286W, N279D+Y286F, N279D+L288I, N279D+E290A,N279D+L294P, N279D+L294K, N279D+L294I, N279D+L294R, N279D+L294V,N279D+L294H, N279D+S295K, N279D+S295V, N279D+S295P, N279D+S295L,N279D+S295R, N279D+S295A, N279D+S295N, N279D+S295M, N279D+S295I,N279D+T296S, N279D+F298Y, W260Y+N279E, W260L+N279E, W260T+N279E,N279E+T280L, N279E+N283W, N279E+N283H, N279E+Y286W, N279E+Y286F,N279E+L288I, N279E+E290A, N279E+L294P, N279E+L294K, N279E+L294I,N279E+L294R, N279E+L294V, N279E+L294H, N279E+S295K, N279E+S295V,N279E+S295P, N279E+S295L, N279E+S295R, N279E+S295A, N279E+S295N,N279E+S295M, N279E+S295I, N279E+T296S, N279E+F298Y, W260Y+T280L,W260L+T280L, W260T+T280L, T280L+N283W, T280L+N283H, T280L+Y286W,T280L+Y286F, T280L+L288I, T280L+E290A, T280L+L294P, T280L+L294K,T280L+L294I, T280L+L294R, T280L+L294V, T280L+L294H, T280L+S295K,T280L+S295V, T280L+S295P, T280L+S295L, T280L+S295R, T280L+S295A,T280L+S295N, T280L+S295M, T280L+S295I, T280L+T296S, T280L+F298Y,W260Y+N283W, W260L+N283W, W260T+N283W, N283W+Y286W, N283W+Y286F,N283W+L288I, N283W+E290A, N283W+L294P, N283W+L294K, N283W+L294I,N283W+L294R, N283W+L294V, N283W+L294H, N283W+S295K, N283W+S295V,N283W+S295P, N283W+S295L, N283W+S295R, N283W+S295A, N283W+S295N,N283W+S295M, N283W+S295I, N283W+T296S, N283W+F298Y, W260Y+N283H,W260L+N283H, W260T+N283H, N283H+Y286W, N283H+Y286F, N283H+L288I,N283H+E290A, N283H+L294P, N283H+L294K, N283H+L294I, N283H+L294R,N283H+L294V, N283H+L294H, N283H+S295K, N283H+S295V, N283H+S295P,N283H+S295L, N283H+S295R, N283H+S295A, N283H+S295N, N283H+S295M,N283H+S295I, N283H+T296S, W260Y+Y286W, W260L+Y286W, W260T+Y286W,Y286W+L288I, Y286W+E290A, Y286W+L294P, Y286W+L294K, Y286W+L294I,Y286W+L294R, Y286W+L294V, Y286W+L294H, Y286W+S295K, Y286W+S295V,Y286W+S295P, Y286W+S295L, Y286W+S295R, Y286W+S295A, Y286W+S295N,Y286W+S295M, Y286W+S295I, Y286W+T296S, Y286W+F298Y, W260Y+Y286F,W260L+Y286F, W260T+Y286F, Y286F+L288I, Y286F+E290A, Y286F+L294P,Y286F+L294K, Y286F8+L294I, Y286F+L294R, Y286F+L294V, Y286F+L294H,Y286F+S295K, Y286F+S295V, Y286F+S295P, Y286F+S295L, Y286F+S295R,Y286F+S295A, Y286F+S295N, Y286F+S295M, Y286F+S295I, Y286F+T296S,Y286F+F298Y, W260Y+L288I, W260L+L288I, W260T+L288I, L288I+E290A,L288I+L294P, L288I+L294K, L288I+L294I, L288I+L294R, L288I+L294V,L288I+L294H, L288I+S295K, L288I+S295V, L288I+S295P, L288I+S295L,L288I+S295R, L288I+S295A, L288I+S295N, L288I+S295M, L288I+S295I,L288I+T296S, L288I+F298Y, W260Y+E290A, W260L+E290A, W260T+E290A,E290A+L294P, E290A+L294K, E290A+L294I, E290A+L294R, E290A+L294V,E290A+L294H, E290A+S295K, E290A+S295V, E290A+S295P, E290A+S295L,E290A+S295R, E290A+S295A, E290A+S295N, E290A+S295M, E290A+S295I,E290A+T296S, E290A+F298Y, W260Y+S294P, W260L+S294P, W260T+S294P,L294P+S295K, L294P+S295V, L294P+S295P, L294P+S295L, L294P+S295R,L294P+S295A, L294P+S295N, L294P+S295M, L294P+S295I, L294P+T296S,L294P+F298Y, W260Y+L294K, W260L+L294K, W260T+L294K, L294K+S295K,L294K+S295V, L294K+S295P, L294K+S295L, L294K+S295R, L294K+S295A,L294K+S295N, L294K+S295M, L294K+S295I, L294K+T296S, L294K+F298Y,W260Y+L294I, W260L+L294I, W260T+L294I, L294I+S295K, L294I+S295V,L294I+S295P, L294I+S295L, L294I+S295R, L294I+S295A, L294I+S295N,L294I+S295M, L294I+S295I, L294I+T296S, L294I+F298Y, W260Y+L294R,W260L+L294R, W260T+L294R, L294R+S295K, L294R+S295V, L294R+S295P,L294R+S295L, L294R+S295R, L294R+S295A, L294R+S295N, L294R+S295M,L294R+S295I, L294R+T296S, L294R+F298Y, W260Y+L294V, W260L+L294V,W260T+L294V, L294V+S295K, L294V+S295V, L294V+S295P, L294V+S295L,L294V+S295R, L294V+S295A, L294V+S295N, L294V+S295M, L294V+S295I,L294V+T296S, L294V+F298Y, W260Y+L294H, W260L+L294H, W260T+L294H,L294H+S295K, L294H+S295V, L294H+S295P, L294H+S295L, L294H+S295R,L294H+S295A, L294H+S295N, L294H+S295M, L294H+S295I, L294H+T296S,L294H+F298Y, W260Y+S295K, W260L+S295K, W260T+S295K, S295K+T296S,S295K+F298Y, W260Y+S295V, W260L+S295V, W260T+S295V, S295V+T296S,S295V+F298Y, W260Y+S295P, W260L+S295P, W260T+S295P, S295P+T296S,S295P+F298Y, W260Y+S295L, W260L+S295L, W260T+S295L, S295L+T296S,S295L+F298Y, W260Y+S295R, W260L+S295R, W260T+S295R, S295R+T296S,S295R+F298Y, W260Y+S295A, W260L+S295A, W260T+S295A, S295A+T296S,S295A+F298Y, W260Y+S295N, W260L+S295N, W260T+S295N, S295N+T296S,S295N+F298Y, W260Y+S295M, W260L+S295M, W260T+S295M, S295M+T296S,S295M+F298Y, W260Y+S295I, W260L+S295I, W260T+S295I, S295I+T296S,S295I+F298Y, W260Y+T296S, W260L+T296S, W260T+T296S, T296S+F298Y,W260Y+F298Y, W260L+F298Y, and W260T+F298Y.

In an embodiment, the variant has sequence identity of at least 60%,e.g., at least 62, at least 63%, at least 64%, at least 65%, at least70%, at least 75%, at least 80%, at least 85%, at least 90%, at least91%, at least 92%, at least 93%, at least 94%, at least 95%, at least96%, at least 97%, at least 98%, or at least 99%, but less than 100%, tothe amino acid sequence of the parent mannanase.

In another embodiment, the variant has at least 60%, e.g., at least 62,at least 63%, at least 64%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, such as at least 96%, at least97%, at least 98%, or at least 99%, but less than 100%, sequenceidentity to the mature polypeptide of SEQ ID NO: 2.

As described above the stability, such as the in-detergent stability orthermostability, may be determined as described in the Examples.

Thus, in one embodiment, the variant of the present invention has animproved stability when measured at pH 9.0, 10.5, and/or 10.8. Inparticular, the stability may be determined at a pH of 9.0.

Accordingly, in one embodiment, the variant is selected from the list ofvariants shown in the Examples.

Stability may not only be measured at pH 9.0 but may also be measured ateither more alcaline or acidic pH. The pH that stability is measured atmay vary depending on the detergent composition the variant (or enzyme)needs to be stable in. Thus, the present invention also encompassstability at other pH, such as pH 10.8. Thus, in one embodiment, thevariant of the present invention has an improved stability when measuredat pH 10.8.

In one embodiment, the improved stability of the variant of the presentinvention is measured either at pH 9.0 or 10.8, or the improvedstability is seen at both pHs, i.e. pH 9.0 and pH 10.8. Thus in oneembodiment, the variant has an improved stability compared to the parentmannanase, when the stability is measured at pH 9.0 and/or pH 10.8.

In one embodiment, the variant has an Improvement Factor of at least 3.0for a measure of stability at pH 9.0, pH 10.5, and/or pH 10.8.

The amino acid changes may be of a minor nature, that is conservativeamino acid substitutions or insertions that do not significantly affectthe folding and/or activity of the protein; small deletions, typicallyof 1-30 amino acids; small amino- or carboxyl-terminal extensions, suchas an amino-terminal methionine residue; a small linker peptide of up to20-25 residues; or a small extension that facilitates purification bychanging net charge or another function, such as a poly-histidine tract,an antigenic epitope or a binding domain.

Examples of conservative substitutions are within the groups of basicamino acids (arginine, lysine and histidine), acidic amino acids(glutamic acid and aspartic acid), polar amino acids (glutamine andasparagine), hydrophobic amino acids (leucine, isoleucine and valine),aromatic amino acids (phenylalanine, tryptophan and tyrosine), and smallamino acids (glycine, alanine, serine, threonine and methionine). Aminoacid substitutions that do not generally alter specific activity areknown in the art and are described, for example, by H. Neurath and R. L.Hill, 1979, In, The Proteins, Academic Press, New York. Commonsubstitutions are Ala/Ser, Val/Ile, Asp/Glu, Thr/Ser, Ala/Gly, Ala/Thr,Ser/Asn, Ala/Val, Ser/Gly, Tyr/Phe, Ala/Pro, Lys/Arg, Asp/Asn, Leu/Ile,LeuNal, Ala/Glu, and Asp/Gly.

Alternatively, the amino acid changes are of such a nature that thephysico-chemical properties of the polypeptides are altered. Forexample, amino acid changes may improve the thermal stability of thepolypeptide, alter the substrate specificity, change the pH optimum, andthe like.

In another embodiment, the variant comprises a substitution in theposition corresponding to position 260 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of W260F, W260L, W260Y, andW260T.

In another embodiment, the variant comprises a substitution in theposition corresponding to position 288 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is L288I.

In another embodiment, the variant comprises a substitution in theposition corresponding to position 294 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of L294P, L294K, L294I,L294R, L294V, and L294H.

In another embodiment, the variant comprises a substitution in theposition corresponding to position 295 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of S295K, S295V, S295P,S295L, S295R, S295A, S295N, S295M, and S295I.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 1 of the polypeptide of SEQ ID NO: 2,or of a polypeptide having at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of A1G and A1V.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 2 of the polypeptide of SEQ ID NO: 2,or of a polypeptide having at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is N2E.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 3 of the polypeptide of SEQ ID NO: 2,or of a polypeptide having at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is S3P.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 4 of the polypeptide of SEQ ID NO: 2,or of a polypeptide having at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is G4D.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 5 of the polypeptide of SEQ ID NO: 2,or of a polypeptide having at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is F5H.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 6 of the polypeptide of SEQ ID NO: 2,or of a polypeptide having at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of Y6H, Y6M, Y6F, Y6W, andY6H.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 8 of the polypeptide of SEQ ID NO: 2,or of a polypeptide having at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of S8T, S8P, and S8R.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 11 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of T11K, and T11R.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 13 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is Y13F.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 14 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of D14S and D14K.

In another embodiment, the variant comprises or consists of asubstitution in the position corresponding to position 18 of thepolypeptide of SEQ ID NO: 2, or of a polypeptide having at least 65%, atleast 70%, at least 75%, at least 80%, at least 85%, at least 90%, atleast 91%, at least 92%, at least 93%, at least 94%, at least 95%, atleast 96%, at least 97%, at least 98%, at least 99% identity to thepolypeptide of SEQ ID NO: 2 which has mannanase activity, and furtherthe variant has improveds stability compared to the mannanase of SEQ IDNO: 2. In one embodiment, the substitution is selected from the group ofN18V and N18R.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 30 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is A30T.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 32 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of Y32F and Y32W.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 33 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is K33Q.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 34 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is D34G.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 35 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is Q35L.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 37 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is T37P.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 41 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of E41V and E41N.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 45 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is N45G.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 47 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of G47S and G47A.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 57 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is D57N.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 59 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is G59Q.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 60 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is Q60R.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 63 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of K63R and K63Q.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 65 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is D65E.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 70 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is R70K.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 71 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is N71S.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 74 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is S74K.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 77 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of E77T and E77N.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 78 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is D78G.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 80 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is H80K.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 82 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of V82R, V82I and V82S.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 83 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of A83P and A83S.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 93 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of Y93Q and Y93A.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 95 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is S95D.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 97 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is A97R.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 98 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is S98D.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 100 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is N100Y.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 104 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of D104A and D104G.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 108 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is E108S.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 111 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of S111A, S111K, and S111R.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 114 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of I114Q, I114M, and I114W.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 116 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is K116R.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 118 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is D118K.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 119 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is T119R.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 131 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is S131T.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 133 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of E133R and E133Q.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 135 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is D135P.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 136 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is A136P.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 139 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of D139R and D139A.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 142 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of K142R, K142M, K142S, andK142V.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 143 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is Q143R.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 150 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of N150R, N150T, and N150S.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 169 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of Q169A, Q169R, and Q169K.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 172 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is H172R.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 174 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of Y174R, Y174L, Y174W, andY174F.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 176 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is R176Q.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 177 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of E177S and E177Y.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 180 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is N180R.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 183 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of P183T and P183G.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 184 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of Q184E and Q184K.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 185 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is R185G.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 196 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of Y196W or Y196F.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 200 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is N200T.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 202 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is S202R.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 203 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is Q203T.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 205 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is R205K.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 210 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of R210M, R210G, and R210L.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 213 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of N213V and N213D.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 228 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is T228S.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 229 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is N229D.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 234 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of E234F and E234Y.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 235 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of A235R and A235K.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 241 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is S241C.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 243 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of Q243E and Q243K.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 244 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of R244K and R244V.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 250 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is A250G.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 254 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is K254Y.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 257 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of G257W, G257E, G257A, andG257G.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 260 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is W260F.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 262 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is Y262F.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 266 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is S266A.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 268 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is D268N.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 270 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is A270D.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 184 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of N272M and N272T.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 273 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of N273E and N273D.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 276 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of A276E, A276D, and A276W.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 279 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of N279D and N279E.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 280 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is T280L.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 283 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of N283H and N283W.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 286 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of Y286W and Y286F.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 288 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is L288I.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 290 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is E290A.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 294 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of L294R, L294V, L294P,L294H, L294K, and L294I.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 295 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is selected from the group of S295I, S295K, S295A,S295M, S295N, S295V, S295P, S295L, and S295R.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 296 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is T296S.

In another embodiment, the second substitution is a substitution in theposition corresponding to position 298 of the polypeptide of SEQ ID NO:2, or of a polypeptide having at least 65%, at least 70%, at least 75%,at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 94%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99% identity to the polypeptide of SEQ ID NO: 2which has mannanase activity, and further the variant has improvedsstability compared to the mannanase of SEQ ID NO: 2. In one embodiment,the substitution is F298Y.

Essential amino acids in a polypeptide can be identified according toprocedures known in the art, such as site-directed mutagenesis oralanine-scanning mutagenesis (Cunningham and Wells, 1989, Science 244:1081-1085). In the latter technique, single alanine mutations areintroduced at every residue in the molecule, and the resultant mutantmolecules are tested for mannanase activity to identify amino acidresidues that are critical to the activity of the molecule. See also,Hilton et al., 1996, J. Biol. Chem. 271: 4699-4708. The active site ofthe enzyme or other biological interaction can also be determined byphysical analysis of structure, as determined by such techniques asnuclear magnetic resonance, crystallography, electron diffraction, orphotoaffinity labeling, in conjunction with mutation of putative contactsite amino acids. See, for example, de Vos et al., 1992, Science 255:306-312; Smith et al., 1992, J. Mol. Biol. 224: 899-904; Wlodaver etal., 1992, FEBS Lett. 309: 59-64. The identity of essential amino acidscan also be inferred from an alignment with a related polypeptide.

The variants may consist of 250 to 300, e.g., 260 to 300, 270 to 300,285 to 300 amino acids.

In an embodiment, the variant has improved specific activity compared tothe parent enzyme.

In an embodiment, the variant has improved stability under storageconditions compared to the parent enzyme.

In an embodiment, the variant has improved thermal activity compared tothe parent enzyme.

In an embodiment, the variant has improved thermostability compared tothe parent enzyme.

In an alternative aspect, the present invention relates to an isolatedmannanase variant of a parent mannannase, wherein the variant comprisesat least two substitutions in any two or more positions corresponding topositions selected from the group of 3, 37, 47, 77, 82, 83, 93, 98, 116,135, 136, 241, 257, and 258, wherein numbering is according to SEQ IDNO: 2, said variant has mannanase activity and has at least 60%, e.g.,at least 62%, at least 63%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 95%, at least 96%, atleast 97%, at least 98%, or at least 99%, but less than 100% sequenceidentity to the mature polypeptide of SEQ ID NO: 1 or the polypeptide ofSEQ ID NO: 2.

In one specific embodiment, the variant comprises at least two of thesubstitutions selected from the group of: S3P, T37P, G47A, G47S, E77T,V82I, V82R, A83P, Y93Q, Y93C, Y93A, Y93F, Y93I, Y93R, S98P, K116R,D135P, A136P, S241C, G257W, G257E, G257L, G257A, G257S, G257Y, G257F,and P258Q.

Such alternative variants have been shown to have an improved stabilityas compared to the parent mannanase.

Parent Mannanases

The parent mannanase may be (a) a polypeptide having at least 58%, suchas at least 65% sequence identity to the mature polypeptide of SEQ IDNO: 1; (b) a polypeptide encoded by a polynucleotide that hybridizesunder low stringency conditions with (i) the mature polypeptide codingsequence of SEQ ID NO: 3, (ii) the full-length complement of (i); or (c)a polypeptide encoded by a polynucleotide having at least 58%, such asat least 65% sequence identity to the mature polypeptide coding sequenceof SEQ ID NO: 3.

In an aspect, the parent mannanase has a sequence identity to the maturepolypeptide of SEQ ID NO: 1 of at least 58%, such as at least 65%, e.g.,at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, atleast 91%, at least 92%, at least 93%, at least 94%, at least 95%, atleast 96%, at least 97%, at least 98%, at least 99%, or 100%, which hasmannanase activity. In one aspect, the amino acid sequence of the parentmannanase differs by up to 20 amino acids, e.g., 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 from the maturepolypeptide of SEQ ID NO: 1.

In an aspect, the parent mannanase has a sequence identity to thepolypeptide of SEQ ID NO: 2 of at least 58%, such as at least 65%, e.g.,at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, atleast 91%, at least 92%, at least 93%, at least 94%, at least 95%, atleast 96%, at least 97%, at least 98%, at least 99%, or 100%, which hasmannanase activity. In one aspect, the amino acid sequence of the parentmannanase differs by up to 20 amino acids, e.g., 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 from the maturepolypeptide of SEQ ID NO: 2.

In another aspect, the parent comprises or consists of the amino acidsequence of SEQ ID NO: 2. In another aspect, the parent comprises orconsists of the mature polypeptide of SEQ ID NO: 1.

In another aspect, the parent is a fragment of the polypeptide of SEQ IDNO: 2 containing at least 250 amino acid residues, e.g., at least 270and at least 290 amino acid residues.

In another embodiment, the parent is an allelic variant of thepolypeptide of SEQ ID NO: 2.

In another aspect, the parent is encoded by a polynucleotide thathybridizes under very low stringency conditions, low stringencyconditions, medium stringency conditions, medium-high stringencyconditions, high stringency conditions, or very high stringencyconditions with (i) the mature polypeptide coding sequence of SEQ ID NO:3, or (ii) the full-length complement of (i) or (ii) (Sambrook et al.,1989, Molecular Cloning, A Laboratory Manual, 2d edition, Cold SpringHarbor, N.Y.).

The polynucleotide of SEQ ID NO: 3 or a subsequence thereof, as well asthe polypeptide of SEQ ID NO: 2 or a fragment thereof, may be used todesign nucleic acid probes to identify and clone DNA encoding a parentfrom strains of different genera or species according to methods wellknown in the art. In particular, such probes can be used forhybridization with the genomic DNA or cDNA of a cell of interest,following standard Southern blotting procedures, in order to identifyand isolate the corresponding gene therein. Such probes can beconsiderably shorter than the entire sequence, but should be at least15, e.g., at least 25, at least 35, or at least 70 nucleotides inlength. Preferably, the nucleic acid probe is at least 100 nucleotidesin length, e.g., at least 200 nucleotides, at least 300 nucleotides, atleast 400 nucleotides, at least 500 nucleotides, at least 600nucleotides, at least 700 nucleotides, at least 800 nucleotides, or atleast 900 nucleotides in length. Both DNA and RNA probes can be used.The probes are typically labeled for detecting the corresponding gene(for example, with ³²P, ³H, ³⁵S, biotin, or avidin). Such probes areencompassed by the present invention.

A genomic DNA or cDNA library prepared from such other strains may bescreened for DNA that hybridizes with the probes described above andencodes a parent. Genomic or other DNA from such other strains may beseparated by agarose or polyacrylamide gel electrophoresis, or otherseparation techniques. DNA from the libraries or the separated DNA maybe transferred to and immobilized on nitrocellulose or other suitablecarrier material. In order to identify a clone or DNA that hybridizeswith SEQ ID NO: 1 or a subsequence thereof, the carrier material is usedin a Southern blot.

For purposes of the present invention, hybridization indicates that thepolynucleotide hybridizes to a labeled nucleic acid probe correspondingto (i) SEQ ID NO: 3; (ii) the mature polypeptide coding sequence of SEQID NO: 3; (iii) the full-length complement thereof; or (iv) asubsequence thereof; under very low to very high stringency conditions.Molecules to which the nucleic acid probe hybridizes under theseconditions can be detected using, for example, X-ray film or any otherdetection means known in the art.

In one aspect, the nucleic acid probe is the mature polypeptide codingsequence of SEQ ID NO: 3. In another aspect, the nucleic acid probe is apolynucleotide that encodes the polypeptide of SEQ ID NO: 1; the maturepolypeptide thereof; or a fragment thereof. In another aspect, thenucleic acid probe is SEQ ID NO: 3.

In another embodiment, the parent is encoded by a polynucleotide havinga sequence identity to the mature polypeptide coding sequence of SEQ IDNO: 3 of at least 58%, such as at least 65%, e.g., at least 70%, atleast 75%, at least 80%, at least 85%, at least 90%, at least 91%, atleast 92%, at least 93%, at least 94%, at least 95%, at least 96%, atleast 97%, at least 98%, at least 99%, or 100%.

The polypeptide may be a hybrid polypeptide in which a region of onepolypeptide is fused at the N-terminus or the C-terminus of a region ofanother polypeptide.

The parent may be a fusion polypeptide or cleavable fusion polypeptidein which another polypeptide is fused at the N-terminus or theC-terminus of the polypeptide of the present invention. A fusionpolypeptide is produced by fusing a polynucleotide encoding anotherpolypeptide to a polynucleotide of the present invention. Techniques forproducing fusion polypeptides are known in the art, and include ligatingthe coding sequences encoding the polypeptides so that they are in frameand that expression of the fusion polypeptide is under control of thesame promoter(s) and terminator. Fusion polypeptides may also beconstructed using intein technology in which fusion polypeptides arecreated post-translationally (Cooper et al., 1993, EMBO J. 12:2575-2583; Dawson et al., 1994, Science 266: 776-779).

A fusion polypeptide can further comprise a cleavage site between thetwo polypeptides. Upon secretion of the fusion protein, the site iscleaved releasing the two polypeptides. Examples of cleavage sitesinclude, but are not limited to, the sites disclosed in Martin et al.,2003, J. Ind. Microbiol. Biotechnol. 3: 568-576; Svetina et al., 2000,J. Biotechnol. 76: 245-251; Rasmussen-Wilson et al., 1997, Appl.Environ. Microbiol. 63: 3488-3493; Ward et al., 1995, Biotechnology 13:498-503; and Contreras et al., 1991, Biotechnology 9: 378-381; Eaton etal., 1986, Biochemistry 25: 505-512; Collins-Racie et al., 1995,Biotechnology 13: 982-987; Carter et al., 1989, Proteins: Structure,Function, and Genetics 6: 240-248; and Stevens, 2003, Drug DiscoveryWorld 4: 35-48.

The parent may be obtained from microorganisms of any genus. Forpurposes of the present invention, the term “obtained from” as usedherein in connection with a given source shall mean that the parentencoded by a polynucleotide is produced by the source or by a strain inwhich the polynucleotide from the source has been inserted. In oneaspect, the parent is secreted extracellularly.

The parent may be a bacterial mannanase. For example, the parent may bea Gram-positive bacterial polypeptide such as a Bacillus, Clostridium,Enterococcus, Geobacillus, Lactobacillus, Lactococcus, Oceanobacillus,Staphylococcus, Streptococcus, or Streptomyces mannanase, or aGram-negative bacterial polypeptide such as a Campylobacter, E. coli,Flavobacterium, Fusobacterium, Helicobacter, Ilyobacter, Neisseria,Pseudomonas, Salmonella, or Ureaplasma mannanase.

In one aspect, the parent is a Bacillus alkalophilus, Bacillusamyloliquefaciens, Bacillus brevis, Bacillus circulans, Bacillusclausii, Bacillus coagulans, Bacillus firmus, Bacillus lautus, Bacilluslentus, Bacillus licheniformis, Bacillus megaterium, Bacillus pumilus,Bacillus stearothermophilus, Bacillus subtilis, or Bacillusthuringiensis mannanase.

In another aspect, the parent is a Streptococcus equisimilis,Streptococcus pyogenes, Streptococcus uberis, or Streptococcus equisubsp. Zooepidemicus mannanase.

In another aspect, the parent is a Streptomyces achromogenes,Streptomyces avermitilis, Streptomyces coelicolor, Streptomyces griseus,or Streptomyces lividans mannanase.

In another aspect, the parent is a Bacillus bogoriensis mannanase, e.g.,the mannanase of SEQ ID NO: 1 or the mature polypeptide thereof.

It will be understood that for the aforementioned species, the inventionencompasses both the perfect and imperfect states, and other taxonomicequivalents, e.g., anamorphs, regardless of the species name by whichthey are known. Those skilled in the art will readily recognize theidentity of appropriate equivalents.

Strains of these species are readily accessible to the public in anumber of culture collections, such as the American Type CultureCollection (ATCC), Deutsche Sammlung von Mikroorganismen andZellkulturen GmbH (DSMZ), Centraalbureau Voor Schimmelcultures (CBS),and Agricultural Research Service Patent Culture Collection, NorthernRegional Research Center (NRRL).

The parent may be identified and obtained from other sources includingmicroorganisms isolated from nature (e.g., soil, composts, water, etc.)or DNA samples obtained directly from natural materials (e.g., soil,composts, water, etc.) using the above-mentioned probes. Techniques forisolating microorganisms and DNA directly from natural habitats are wellknown in the art. A polynucleotide encoding a parent may then beobtained by similarly screening a genomic DNA or cDNA library of anothermicroorganism or mixed DNA sample. Once a polynucleotide encoding aparent has been detected with the probe(s), the polynucleotide can beisolated or cloned by utilizing techniques that are known to those ofordinary skill in the art (see, e.g., Sambrook et al., 1989, supra).

Preparation of Variants

The present invention also relates to methods for obtaining a varianthaving mannanase activity, comprising: (a) introducing into a parentmannanase at least two substitutions, wherein (a) said firstsubstitution is in an amino acid position selected from the positions260, 288, 294, or 295, and (b) said at least second substitution isselected from any other position in said variant, wherein numbering isaccording to SEQ ID NO: 2, said variant has mannanase activity and hasat least 58%, such as at least 60%, e.g., at least 62%, at least 63%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90%, at least 95%, at least 96%, at least 97%, at least 98%, or atleast 99%, but less than 100% sequence identity to the maturepolypeptide of SEQ ID NO: 1 or the polypeptide of SEQ ID NO: 2, whereinthe variant has mannanase activity; and (b) recovering the variant.

The variants can be prepared using any mutagenesis procedure known inthe art, such as site-directed mutagenesis, synthetic gene construction,semi-synthetic gene construction, random mutagenesis, shuffling, etc.

Site-directed mutagenesis is a technique in which one or more (e.g.,several) mutations are introduced at one or more defined sites in apolynucleotide encoding the parent.

Site-directed mutagenesis can be accomplished in vitro by PCR involvingthe use of oligonucleotide primers containing the desired mutation.Site-directed mutagenesis can also be performed in vitro by cassettemutagenesis involving the cleavage by a restriction enzyme at a site inthe plasmid comprising a polynucleotide encoding the parent andsubsequent ligation of an oligonucleotide containing the mutation in thepolynucleotide. Usually the restriction enzyme that digests the plasmidand the oligonucleotide is the same, permitting sticky ends of theplasmid and the insert to ligate to one another. See, e.g., Scherer andDavis, 1979, Proc. Natl. Acad. Sci. USA 76: 4949-4955; and Barton etal., 1990, Nucleic Acids Res. 18: 7349-4966.

Site-directed mutagenesis can also be accomplished in vivo by methodsknown in the art. See, e.g., U.S. Patent Application Publication No.2004/0171154; Storici et al., 2001, Nature Biotechnol. 19: 773-776; Krenet al., 1998, Nat. Med. 4: 285-290; and Calissano and Macino, 1996,Fungal Genet. Newslett. 43: 15-16.

Any site-directed mutagenesis procedure can be used in the presentinvention. There are many commercial kits available that can be used toprepare variants.

Synthetic gene construction entails in vitro synthesis of a designedpolynucleotide molecule to encode a polypeptide of interest. Genesynthesis can be performed utilizing a number of techniques, such as themultiplex microchip-based technology described by Tian et al. (2004,Nature 432: 1050-1054) and similar technologies wherein oligonucleotidesare synthesized and assembled upon photo-programmable microfluidicchips.

Single or multiple amino acid substitutions, deletions, and/orinsertions can be made and tested using known methods of mutagenesis,recombination, and/or shuffling, followed by a relevant screeningprocedure, such as those disclosed by Reidhaar-Olson and Sauer, 1988,Science 241: 53-57; Bowie and Sauer, 1989, Proc. Natl. Acad. Sci. USA86: 2152-2156; WO 95/17413; or WO 95/22625. Other methods that can beused include error-prone PCR, phage display (e.g., Lowman et al., 1991,Biochemistry 30: 10832-10837; U.S. Pat. No. 5,223,409; WO 92/06204) andregion-directed mutagenesis (Derbyshire et al., 1986, Gene 46: 145; Neret al., 1988, DNA 7: 127).

Mutagenesis/shuffling methods can be combined with high-throughput,automated screening methods to detect activity of cloned, mutagenizedpolypeptides expressed by host cells (Ness et al., 1999, NatureBiotechnology 17: 893-896). Mutagenized DNA molecules that encode activepolypeptides can be recovered from the host cells and rapidly sequencedusing standard methods in the art. These methods allow the rapiddetermination of the importance of individual amino acid residues in apolypeptide.

Semi-synthetic gene construction is accomplished by combining aspects ofsynthetic gene construction, and/or site-directed mutagenesis, and/orrandom mutagenesis, and/or shuffling. Semi-synthetic construction istypified by a process utilizing polynucleotide fragments that aresynthesized, in combination with PCR techniques. Defined regions ofgenes may thus be synthesized de novo, while other regions may beamplified using site-specific mutagenic primers, while yet other regionsmay be subjected to error-prone PCR or non-error prone PCRamplification. Polynucleotide subsequences may then be shuffled.

Polynucleotides

The present invention also relates to isolated polynucleotides encodinga variant of the present invention. Thus, in one aspect, the presentinvention relates to a polynucleotide encoding a variant comprises atleast two substitutions, wherein (a) said first substitution is in anamino acid position selected from the positions 260, 288, 294, or 295,and (b) said at least second substitution is selected from any otherposition in said variant, wherein numbering is according to SEQ ID NO:2, said variant has mannanase activity and has at least 58%, such as atleast 60%, e.g., at least 62%, at least 63%, at least 65%, at least 70%,at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, atleast 96%, at least 97%, at least 98%, or at least 99%, but less than100% sequence identity to the mature polypeptide of SEQ ID NO: 1 or thepolypeptide of SEQ ID NO: 2.

Nucleic Acid Constructs

The present invention also relates to nucleic acid constructs comprisinga polynucleotide encoding a variant of the present invention operablylinked to one or more control sequences that direct the expression ofthe coding sequence in a suitable host cell under conditions compatiblewith the control sequences. Thus, in one aspect, the present inventionrelates to a polynucleotide encoding a variant comprises at least twosubstitutions, wherein (a) said first substitution is in an amino acidposition selected from the positions 260, 288, 294, or 295, and (b) saidat least second substitution is selected from any other position in saidvariant, wherein numbering is according to SEQ ID NO: 2, said varianthas mannanase activity and has at least 58%, such as at least 60%, e.g.,at least 62%, at least 63%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 95%, at least 96%, atleast 97%, at least 98%, or at least 99%, but less than 100% sequenceidentity to the mature polypeptide of SEQ ID NO: 1 or the polypeptide ofSEQ ID NO: 2, operably linked to one or more control sequences thatdirect the expression of the coding sequence in a suitable host cellunder conditions compatible with the control sequences.

The polynucleotide may be manipulated in a variety of ways to providefor expression of a variant. Manipulation of the polynucleotide prior toits insertion into a vector may be desirable or necessary depending onthe expression vector. The techniques for modifying polynucleotidesutilizing recombinant DNA methods are well known in the art.

The control sequence may be a promoter, a polynucleotide which isrecognized by a host cell for expression of the polynucleotide. Thepromoter contains transcriptional control sequences that mediate theexpression of the variant. The promoter may be any polynucleotide thatshows transcriptional activity in the host cell including mutant,truncated, and hybrid promoters, and may be obtained from genes encodingextracellular or intracellular polypeptides either homologous orheterologous to the host cell.

Examples of suitable promoters for directing transcription of thenucleic acid constructs of the present invention in a bacterial hostcell are the promoters obtained from the Bacillus amyloliquefaciensalpha-amylase gene (amyQ), Bacillus licheniformis alpha-amylase gene(amyL), Bacillus licheniformis penicillinase gene (penP), Bacillusstearothermophilus maltogenic amylase gene (amyM), Bacillus subtilislevansucrase gene (sacB), Bacillus subtilis xylA and xylB genes,Bacillus thuringiensis cryIIIA gene (Agaisse and Lereclus, 1994,Molecular Microbiology 13: 97-107), E. coli lac operon, E. coli trcpromoter (Egon et al., 1988, Gene 69: 301-315), Streptomyces coelicoloragarase gene (dagA), and prokaryotic beta-lactamase gene (Villa-Kamaroffet al., 1978, Proc. Natl. Acad. Sci. USA 75: 3727-3731), as well as thetac promoter (DeBoer et al., 1983, Proc. Natl. Acad. Sci. USA 80:21-25). Further promoters are described in “Useful proteins fromrecombinant bacteria” in Gilbert et al., 1980, Scientific American 242:74-94; and in Sambrook et al., 1989, supra. Examples of tandem promotersare disclosed in WO 99/43835.

The control sequence may also be a transcription terminator, which isrecognized by a host cell to terminate transcription. The terminatorsequence is operably linked to the 3′-terminus of the polynucleotideencoding the variant. Any terminator that is functional in the host cellmay be used.

Preferred terminators for bacterial host cells are obtained from thegenes for Bacillus clausii alkaline protease (aprH), Bacilluslicheniformis alpha-amylase (amyL), and Escherichia coli ribosomal RNA(rrnB).

The control sequence may also be an mRNA stabilizer region downstream ofa promoter and upstream of the coding sequence of a gene which increasesexpression of the gene.

Examples of suitable mRNA stabilizer regions are obtained from aBacillus thuringiensis cryIIIA gene (WO 94/25612) and a Bacillussubtilis SP82 gene (Hue et al., 1995, Journal of Bacteriology 177:3465-3471).

The control sequence may also be a leader, a nontranslated region of anmRNA that is important for translation by the host cell. The leadersequence is operably linked to the 5′-terminus of the polynucleotideencoding the variant. Any leader that is functional in the host cell maybe used.

The control sequence may also be a polyadenylation sequence, a sequenceoperably linked to the 3′-terminus of the variant-encoding sequence and,when transcribed, is recognized by the host cell as a signal to addpolyadenosine residues to transcribed mRNA. Any polyadenylation sequencethat is functional in the host cell may be used.

Preferred polyadenylation sequences for filamentous fungal host cellsare obtained from the genes for Aspergillus nidulans anthranilatesynthase, Aspergillus niger glucoamylase, Aspergillus nigeralpha-glucosidase, Aspergillus oryzae TAKA amylase, and Fusariumoxysporum trypsin-like protease.

Useful polyadenylation sequences for yeast host cells are described byGuo and Sherman, 1995, Mol. Cellular Biol. 15: 5983-5990.

The control sequence may also be a signal peptide coding region thatencodes a signal peptide linked to the N-terminus of a variant anddirects the variant into the cell's secretory pathway. The 5′-end of thecoding sequence of the polynucleotide may inherently contain a signalpeptide coding sequence naturally linked in translation reading framewith the segment of the coding sequence that encodes the variant.Alternatively, the 5′-end of the coding sequence may contain a signalpeptide coding sequence that is foreign to the coding sequence. Aforeign signal peptide coding sequence may be required where the codingsequence does not naturally contain a signal peptide coding sequence.Alternatively, a foreign signal peptide coding sequence may simplyreplace the natural signal peptide coding sequence in order to enhancesecretion of the variant. However, any signal peptide coding sequencethat directs the expressed variant into the secretory pathway of a hostcell may be used.

Effective signal peptide coding sequences for bacterial host cells arethe signal peptide coding sequences obtained from the genes for BacillusNCIB 11837 maltogenic amylase, Bacillus licheniformis subtilisin,Bacillus licheniformis beta-lactamase, Bacillus stearothermophilusalpha-amylase, Bacillus stearothermophilus neutral proteases (nprT,nprS, nprM), and Bacillus subtilis prsA. Further signal peptides aredescribed by Simonen and Palva, 1993, Microbiological Reviews 57:109-137.

The control sequence may also be a propeptide coding sequence thatencodes a propeptide positioned at the N-terminus of a variant. Theresultant polypeptide is known as a proenzyme or propolypeptide (or azymogen in some cases). A propolypeptide is generally inactive and canbe converted to an active polypeptide by catalytic or autocatalyticcleavage of the propeptide from the propolypeptide. The propeptidecoding sequence may be obtained from the genes for Bacillus subtilisalkaline protease (aprE), Bacillus subtilis neutral protease (nprT),Myceliophthora thermophila laccase (WO 95/33836), Rhizomucor mieheiaspartic proteinase, and Saccharomyces cerevisiae alpha-factor.

Where both signal peptide and propeptide sequences are present, thepropeptide sequence is positioned next to the N-terminus of the variantand the signal peptide sequence is positioned next to the N-terminus ofthe propeptide sequence.

It may also be desirable to add regulatory sequences that regulateexpression of the variant relative to the growth of the host cell.Examples of regulatory systems are those that cause expression of thegene to be turned on or off in response to a chemical or physicalstimulus, including the presence of a regulatory compound. Regulatorysystems in prokaryotic systems include the lac, tac, and trp operatorsystems. In yeast, the ADH2 system or GAL1 system may be used. Infilamentous fungi, the Aspergillus niger glucoamylase promoter,Aspergillus oryzae TAKA alpha-amylase promoter, and Aspergillus oryzaeglucoamylase promoter may be used. Other examples of regulatorysequences are those that allow for gene amplification. In eukaryoticsystems, these regulatory sequences include the dihydrofolate reductasegene that is amplified in the presence of methotrexate, and themetallothionein genes that are amplified with heavy metals. In thesecases, the polynucleotide encoding the variant would be operably linkedwith the regulatory sequence.

Expression Vectors

The present invention also relates to recombinant expression vectorscomprising a polynucleotide encoding a variant of the present invention,a promoter, and transcriptional and translational stop signals. Thus, inone aspect, the present invention relates to recombinant expressionvectors comprising a polynucleotide encoding a variant comprises atleast two substitutions, wherein (a) said first substitution is in anamino acid position selected from the positions 260, 288, 294, or 295,and (b) said at least second substitution is selected from any otherposition in said variant, wherein numbering is according to SEQ ID NO:2, said variant has mannanase activity and has at least 58%, such as atleast 60%, e.g., at least 62%, at least 63%, at least 65%, at least 70%,at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, atleast 96%, at least 97%, at least 98%, or at least 99%, but less than100% sequence identity to the mature polypeptide of SEQ ID NO: 1 or thepolypeptide of SEQ ID NO: 2, a promoter, and transcriptional andtranslational stop signals.

The various nucleotide and control sequences may be joined together toproduce a recombinant expression vector that may include one or moreconvenient restriction sites to allow for insertion or substitution ofthe polynucleotide encoding the variant at such sites. Alternatively,the polynucleotide may be expressed by inserting the polynucleotide or anucleic acid construct comprising the polynucleotide into an appropriatevector for expression. In creating the expression vector, the codingsequence is located in the vector so that the coding sequence isoperably linked with the appropriate control sequences for expression.

The recombinant expression vector may be any vector (e.g., a plasmid orvirus) that can be conveniently subjected to recombinant DNA proceduresand can bring about expression of the polynucleotide. The choice of thevector will typically depend on the compatibility of the vector with thehost cell into which the vector is to be introduced. The vector may be alinear or closed circular plasmid.

The vector may be an autonomously replicating vector, i.e., a vectorthat exists as an extrachromosomal entity, the replication of which isindependent of chromosomal replication, e.g., a plasmid, anextrachromosomal element, a minichromosome, or an artificial chromosome.The vector may contain any means for assuring self-replication.Alternatively, the vector may be one that, when introduced into the hostcell, is integrated into the genome and replicated together with thechromosome(s) into which it has been integrated. Furthermore, a singlevector or plasmid or two or more vectors or plasmids that togethercontain the total DNA to be introduced into the genome of the host cell,or a transposon, may be used.

The vector preferably contains one or more selectable markers thatpermit easy selection of transformed, transfected, transduced, or thelike cells. A selectable marker is a gene the product of which providesfor biocide or viral resistance, resistance to heavy metals, prototrophyto auxotrophs, and the like.

Examples of bacterial selectable markers are Bacillus licheniformis orBacillus subtilis dal genes, or markers that confer antibioticresistance such as ampicillin, chloramphenicol, kanamycin, neomycin,spectinomycin or tetracycline resistance. Suitable markers for yeasthost cells include, but are not limited to, ADE2, HIS3, LEU2, LYS2,MET3, TRP1, and URA3. Selectable markers for use in a filamentous fungalhost cell include, but are not limited to, amdS (acetamidase), argB(ornithine carbamoyltransferase), bar (phosphinothricinacetyltransferase), hph (hygromycin phosphotransferase), niaD (nitratereductase), pyrG (orotidine-5′-phosphate decarboxylase), sC (sulfateadenyltransferase), and trpC (anthranilate synthase), as well asequivalents thereof. Preferred for use in an Aspergillus cell areAspergillus nidulans or Aspergillus oryzae amdS and pyrG genes and aStreptomyces hygroscopicus bar gene.

The vector preferably contains an element(s) that permits integration ofthe vector into the host cell's genome or autonomous replication of thevector in the cell independent of the genome.

For integration into the host cell genome, the vector may rely on thepolynucleotide's sequence encoding the variant or any other element ofthe vector for integration into the genome by homologous ornon-homologous recombination. Alternatively, the vector may containadditional polynucleotides for directing integration by homologousrecombination into the genome of the host cell at a precise location(s)in the chromosome(s). To increase the likelihood of integration at aprecise location, the integrational elements should contain a sufficientnumber of nucleic acids, such as 100 to 10,000 base pairs, 400 to 10,000base pairs, and 800 to 10,000 base pairs, which have a high degree ofsequence identity to the corresponding target sequence to enhance theprobability of homologous recombination. The integrational elements maybe any sequence that is homologous with the target sequence in thegenome of the host cell. Furthermore, the integrational elements may benon-encoding or encoding polynucleotides. On the other hand, the vectormay be integrated into the genome of the host cell by non-homologousrecombination.

For autonomous replication, the vector may further comprise an origin ofreplication enabling the vector to replicate autonomously in the hostcell in question. The origin of replication may be any plasmidreplicator mediating autonomous replication that functions in a cell.The term “origin of replication” or “plasmid replicator” means apolynucleotide that enables a plasmid or vector to replicate in vivo.

Examples of bacterial origins of replication are the origins ofreplication of plasmids pBR322, pUC19, pACYC177, and pACYC184 permittingreplication in E. coli, and pUB110, pE194, pTA1060, and pAMR1 permittingreplication in Bacillus.

More than one copy of a polynucleotide of the present invention may beinserted into a host cell to increase production of a variant. Anincrease in the copy number of the polynucleotide can be obtained byintegrating at least one additional copy of the sequence into the hostcell genome or by including an amplifiable selectable marker gene withthe polynucleotide where cells containing amplified copies of theselectable marker gene, and thereby additional copies of thepolynucleotide, can be selected for by cultivating the cells in thepresence of the appropriate selectable agent.

The procedures used to ligate the elements described above to constructthe recombinant expression vectors of the present invention are wellknown to one skilled in the art (see, e.g., Sambrook et al., 1989,supra).

Host Cells

The present invention also relates to recombinant host cells, comprisinga polynucleotide encoding a variant of the present invention operablylinked to one or more control sequences that direct the production of avariant of the present invention. Thus, in one aspect, the presentinvention relates to recombinant host cells, comprising a polynucleotideencoding a variant comprises at least two substitutions, wherein (a)said first substitution is in an amino acid position selected from thepositions 260, 288, 294, or 295, and (b) said at least secondsubstitution is selected from any other position in said variant,wherein numbering is according to SEQ ID NO: 2, said variant hasmannanase activity and has at least 58%, such as at least 60%, e.g., atleast 62%, at least 63%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 95%, at least 96%, atleast 97%, at least 98%, or at least 99%, but less than 100% sequenceidentity to the mature polypeptide of SEQ ID NO: 1 or the polypeptide ofSEQ ID NO: 2, operably linked to one or more control sequences thatdirec the production of a variant comprises at least two substitutions,wherein (a) said first substitution is in an amino acid positionselected from the positions 260, 288, 294, or 295, and (b) said at leastsecond substitution is selected from any other position in said variant,wherein numbering is according to SEQ ID NO:

2, said variant has mannanase activity and has at least 58%, such as atleast 60%, e.g., at least 62%, at least 63%, at least 65%, at least 70%,at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, atleast 96%, at least 97%, at least 98%, or at least 99%, but less than100% sequence identity to the mature polypeptide of SEQ ID NO: 1 or thepolypeptide of SEQ ID NO: 2.

A construct or vector comprising a polynucleotide is introduced into ahost cell so that the construct or vector is maintained as a chromosomalintegrant or as a self-replicating extra-chromosomal vector as describedearlier. The term “host cell” encompasses any progeny of a parent cellthat is not identical to the parent cell due to mutations that occurduring replication. The choice of a host cell will to a large extentdepend upon the gene encoding the variant and its source.

The host cell may be any cell useful in the recombinant production of avariant, e.g., a prokaryote or a eukaryote.

The prokaryotic host cell may be any Gram-positive or Gram-negativebacterium. Gram-positive bacteria include, but are not limited to,Bacillus, Clostridium, Enterococcus, Geobacillus, Lactobacillus,Lactococcus, Oceanobacillus, Staphylococcus, Streptococcus, andStreptomyces. Gram-negative bacteria include, but are not limited to,Campylobacter, E. coli, Flavobacterium, Fusobacterium, Helicobacter,Ilyobacter, Neisseria, Pseudomonas, Salmonella, and Ureaplasma.

The bacterial host cell may be any Bacillus cell including, but notlimited to, Bacillus alkalophilus, Bacillus amyloliquefaciens, Bacillusbrevis, Bacillus circulans, Bacillus clausii, Bacillus coagulans,Bacillus firmus, Bacillus lautus, Bacillus lentus, Bacilluslicheniformis, Bacillus megaterium, Bacillus pumilus, Bacillusstearothermophilus, Bacillus subtilis, and Bacillus thuringiensis cells.

The bacterial host cell may also be any Streptococcus cell including,but not limited to, Streptococcus equisimilis, Streptococcus pyogenes,Streptococcus uberis, and Streptococcus equi subsp. Zooepidemicus cells.

The bacterial host cell may also be any Streptomyces cell, including,but not limited to, Streptomyces achromogenes, Streptomyces avermitilis,Streptomyces coelicolor, Streptomyces griseus, and Streptomyces lividanscells.

The introduction of DNA into a Bacillus cell may be effected byprotoplast transformation (see, e.g., Chang and Cohen, 1979, Mol. Gen.Genet. 168: 111-115), competent cell transformation (see, e.g., Youngand Spizizen, 1961, J. Bacteriol. 81: 823-829, or Dubnau andDavidoff-Abelson, 1971, J. Mol. Biol. 56: 209-221), electroporation(see, e.g., Shigekawa and Dower, 1988, Biotechniques 6: 742-751), orconjugation (see, e.g., Koehler and Thorne, 1987, J. Bacteriol. 169:5271-5278). The introduction of DNA into an E. coli cell may be effectedby protoplast transformation (see, e.g., Hanahan, 1983, J. Mol. Biol.166: 557-580) or electroporation (see, e.g., Dower et al., 1988, NucleicAcids Res. 16: 6127-6145). The introduction of DNA into a Streptomycescell may be effected by protoplast transformation, electroporation (see,e.g., Gong et al., 2004, Folia Microbiol. (Praha) 49: 399-405),conjugation (see, e.g., Mazodier et al., 1989, J. Bacteriol. 171:3583-3585), or transduction (see, e.g., Burke et al., 2001, Proc. Natl.Acad. Sci. USA 98: 6289-6294). The introduction of DNA into aPseudomonas cell may be effected by electroporation (see, e.g., Choi etal., 2006, J. Microbiol. Methods 64: 391-397), or conjugation (see,e.g., Pinedo and Smets, 2005, Appl. Environ. Microbiol. 71: 51-57). Theintroduction of DNA into a Streptococcus cell may be effected by naturalcompetence (see, e.g., Perry and Kuramitsu, 1981, Infect. Immun. 32:1295-1297), protoplast transformation (see, e.g., Catt and Jollick,1991, Microbios 68: 189-207), electroporation (see, e.g., Buckley etal., 1999, Appl. Environ. Microbiol. 65: 3800-3804) or conjugation (see,e.g., Clewell, 1981, Microbiol. Rev. 45: 409-436). However, any methodknown in the art for introducing DNA into a host cell can be used.

The host cell may also be a eukaryote, such as a mammalian, insect,plant, or fungal cell.

The host cell may be a fungal cell. “Fungi” as used herein includes thephyla Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota as wellas the Oomycota and all mitosporic fungi (as defined by Hawksworth etal., In, Ainsworth and Bisby's Dictionary of The Fungi, 8th edition,1995, CAB International, University Press, Cambridge, UK).

The fungal host cell may be a yeast cell. “Yeast” as used hereinincludes ascosporogenous yeast (Endomycetales), basidiosporogenousyeast, and yeast belonging to the Fungi Imperfecti (Blastomycetes).Since the classification of yeast may change in the future, for thepurposes of this invention, yeast shall be defined as described inBiology and Activities of Yeast (Skinner, Passmore, and Davenport,editors, Soc. App. Bacteriol. Symposium Series No. 9, 1980).

Fungal cells may be transformed by a process involving protoplastformation, transformation of the protoplasts, and regeneration of thecell wall in a manner known per se. Suitable procedures fortransformation of Aspergillus and Trichoderma host cells are describedin EP 238023, Yelton et al., 1984, Proc. Natl. Acad. Sci. USA 81:1470-1474, and Christensen et al., 1988, Bio/Technology 6: 1419-1422.Suitable methods for transforming Fusarium species are described byMalardier et al., 1989, Gene 78: 147-156, and WO 96/00787. Yeast may betransformed using the procedures described by Becker and Guarente, InAbelson, J. N. and Simon, M. I., editors, Guide to Yeast Genetics andMolecular Biology, Methods in Enzymology, Volume 194, pp 182-187,Academic Press, Inc., New York; Ito et al., 1983, J. Bacteriol. 153:163; and Hinnen et al., 1978, Proc. Natl. Acad. Sci. USA 75: 1920.

Methods of Production

The present invention also relates to methods of producing a variant,comprising: (a) cultivating a host cell of the present invention underconditions suitable for expression of the variant; and (b) recoveringthe variant. Thus, in one aspect, the present invention relates tomethods of producing a variant, comprising the steps of (a) cultivatinga host cell comprising a polynucleotide encoding a variant comprises atleast two substitutions, wherein (a) said first substitution is in anamino acid position selected from the positions 260, 288, 294, or 295,and (b) said at least second substitution is selected from any otherposition in said variant, wherein numbering is according to SEQ ID NO:2, said variant has mannanase activity and has at least 58%, such as atleast 60%, e.g., at least 62%, at least 63%, at least 65%, at least 70%,at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, atleast 96%, at least 97%, at least 98%, or at least 99%, but less than100% sequence identity to the mature polypeptide of SEQ ID NO: 1 or thepolypeptide of SEQ ID NO: 2, operably linked to one or more controlsequences that direc the production of a variant under conditionssuitable for expression of the variant; and (b) recovering the variant.

The host cells are cultivated in a nutrient medium suitable forproduction of the variant using methods known in the art. For example,the cell may be cultivated by shake flask cultivation, or small-scale orlarge-scale fermentation (including continuous, batch, fed-batch, orsolid state fermentations) in laboratory or industrial fermentorsperformed in a suitable medium and under conditions allowing the variantto be expressed and/or isolated. The cultivation takes place in asuitable nutrient medium comprising carbon and nitrogen sources andinorganic salts, using procedures known in the art. Suitable media areavailable from commercial suppliers or may be prepared according topublished compositions (e.g., in catalogues of the American Type CultureCollection). If the variant is secreted into the nutrient medium, thevariant can be recovered directly from the medium. If the variant is notsecreted, it can be recovered from cell lysates.

The variant may be detected using methods known in the art that arespecific for the variants, such as a mannanase enzyme assay as describedin Example 2. These detection methods include, but are not limited to,use of specific antibodies, formation of an enzyme product, ordisappearance of an enzyme substrate. For example, an enzyme assay maybe used to determine the activity of the variant.

The variant may be recovered using methods known in the art. Forexample, the variant may be recovered from the nutrient medium byconventional procedures including, but not limited to, collection,centrifugation, filtration, extraction, spray-drying, evaporation, orprecipitation.

The variant may be purified by a variety of procedures known in the artincluding, but not limited to, chromatography (e.g., ion exchange,affinity, hydrophobic, chromatofocusing, and size exclusion),electrophoretic procedures (e.g., preparative isoelectric focusing),differential solubility (e.g., ammonium sulfate precipitation),SDS-PAGE, or extraction (see, e.g., Protein Purification, Janson andRyden, editors, VCH Publishers, New York, 1989) to obtain substantiallypure variants.

In an alternative aspect, the variant is not recovered, but rather ahost cell of the present invention expressing the variant is used as asource of the variant.

Methods or Uses Methods for Improving the Nutritional Value of AnimalFeed

The present invention further relates to a method for improving thenutritional value of an animal feed comprising plant based material,comprising adding to the feed a mannanase variant.

The term improving the nutritional value of an animal feed meansimproving the availability of nutrients in the feed. The nutritionalvalues refers in particular to improving the solubilization anddegradation of the arabinoxylan-containing fraction (e.g., such ashemicellulose) of the feed, thereby leading to increased release ofnutrients from cells in the endosperm that have cell walls composed ofhighly recalcitrant hemicellulose. Consequently, an increased release ofarabinoxylan oligomers indicates a disruption of the cell walls and as aresult the nutritional value of the feed is improved resulting inincreased growth rate and/or weight gain and/or feed conversion (i.e.,the weight of ingested feed relative to weight gain). In addition thearabinoxylan oligomer release may result in improved utilization ofthese components per se either directly or by bacterial fermentation inthe hind gut thereby resulting in a production of short chain fattyacids that may be readily absorbed in the hind and utilised in theenergy metabolism.

Compositions of the Invention

The present invention also relates to compositions comprising apolypeptide variant of the present invention. Accordingly, the presentinvention relates to compositions comprising a variant comprising atleast two substitutions, wherein (a) said first substitution is in anamino acid position selected from the positions 260, 288, 294, or 295,and (b) said at least second substitution is selected from any otherposition in said variant, wherein numbering is according to SEQ ID NO:2, said variant has mannanase activity and has at least 58%, such as atleast 60%, e.g., at least 62%, at least 63%, at least 65%, at least 70%,at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, atleast 96%, at least 97%, at least 98%, or at least 99%, but less than100% sequence identity to the mature polypeptide of SEQ ID NO: 1 or thepolypeptide of SEQ ID NO: 2. Preferably, the compositions are enrichedin such a variant. The term “enriched” means that the alpha-amylaseactivity of the composition has been increased, e.g., with an enrichmentfactor of 1.1.

In one embodiment, the present invention relates to a compositioncomprising a variant comprising at least two substitutions, wherein (a)said first substitution is in an amino acid position selected from thepositions 260, 288, 294, or 295, and (b) said at least secondsubstitution is selected from any other position in said variant,wherein numbering is according to SEQ ID NO: 2, and a protease, such asa protease of SEQ ID NO: 4 or a variant thereof. The protease variantmay be a variant of SEQ ID NO: 4 or any protease having at least 70%sequence identity thereto comprising one or more substitutions selectedfrom the group of substitutions: Y161A, R164S, and A188P, or a variantcomprising one or more substitutions selected from the group: S9E, N42R,N74D, V199I, Q200L, Y203W, S253D, N255W, and L256E.

The composition may comprise a polypeptide variant as the majorenzymatic component, e.g., a mono-component composition. Alternatively,the composition may comprise multiple enzymatic activities, such as anaminopeptidase, amylase, carbohydrase, carboxypeptidase, catalase,cellulase, chitinase, cutinase, cyclodextrin glycosyltransferase,deoxyribonuclease, esterase, alpha-galactosidase, beta-galactosidase,glucoamylase, alpha-glucosidase, beta-glucosidase, haloperoxidase,invertase, laccase, lipase, mannosidase, oxidase, pectinolytic enzyme,peptidoglutaminase, peroxidase, phytase, polyphenoloxidase, proteolyticenzyme, ribonuclease, transglutaminase, or xylanase. The additionalenzyme(s) may be produced, for example, by a microorganism belonging tothe genus Aspergillus, e.g., Aspergillus aculeatus, Aspergillus awamori,Aspergillus foetidus, Aspergillus fumigatus, Aspergillus japonicus,Aspergillus nidulans, Aspergillus niger, or Aspergillus oryzae;Fusarium, e.g., Fusarium bactridioides, Fusarium cerealis, Fusariumcrookwellense, Fusarium culmorum, Fusarium graminearum, Fusariumgraminum, Fusarium heterosporum, Fusarium negundi, Fusarium oxysporum,Fusarium reticulatutn, Fusarium roseum, Fusarium sambucinum, Fusariumsarcochroum, Fusarium sulphureum, Fusarium toruloseum, Fusariumtrichothecioides, or Fusarium venenatum; Humicola, e.g., Humicolainsolens or Humicola lanuginosa; or Trichoderma, e.g., Trichodermaharzianum, Trichoderma koningii, Trichoderma longibrachiatum,Trichoderma reesei, or Trichoderma viride.

The compositions may be prepared in accordance with methods known in theart and may be in the form of a liquid or a dry composition. Forinstance, the composition may be in the form of a granulate or amicrogranulate. The polypeptide variant may be stabilized in accordancewith methods known in the art.

The detergent enzyme(s) may be included in a detergent composition byadding separate additives containing one or more enzymes, or by adding acombined additive comprising all of these enzymes. A detergent additiveof the invention, i.e., a separate additive or a combined additive, canbe formulated, e.g., granulate, a liquid, a slurry, etc. Preferreddetergent additive formulations are granulates, in particularnon-dusting granulates, liquids, in particular stabilized liquids, orslurries. Thus, the present invention also relates to a detergentadditive comprising a variant of the invention, optionally in the formof a non-dusting granulate, stabilized liquid, or protected enzyme.Accordingly, the present invention relates to a detergent additivecomprising variant comprises at least two substitutions, wherein (a)said first substitution is in an amino acid position selected from thepositions 260, 288, 294, or 295, and (b) said at least secondsubstitution is selected from any other position in said variant,wherein numbering is according to SEQ ID NO: 2, said variant hasmannanase activity and has at least 60%, e.g., at least 62%, at least63%, at least 65%, at least 70%, at least 75%, at least 80%, at least85%, at least 90%, at least 95%, at least 96%, at least 97%, at least98%, or at least 99%, but less than 100% sequence identity to the maturepolypeptide of SEQ ID NO: 1 or the polypeptide of SEQ ID NO: 2,optionally, wherein the detergent additive is in the form of anon-dusting granulate, stabilized liquid, or protected enzyme.

In one aspect, the present invention relates to detergent compositionscomprising a polypeptide variant of the present invention in combinationwith one or more additional cleaning composition components.Accordingly, the present invention relates to a detergent compositioncomprising variant comprises at least two substitutions, wherein (a)said first substitution is in an amino acid position selected from thepositions 260, 288, 294, or 295, and (b) said at least secondsubstitution is selected from any other position in said variant,wherein numbering is according to SEQ ID NO: 2, said variant hasmannanase activity and has at least 58%, such as at least 60%, e.g., atleast 62%, at least 63%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 95%, at least 96%, atleast 97%, at least 98%, or at least 99%, but less than 100% sequenceidentity to the mature polypeptide of SEQ ID NO: 1 or the polypeptide ofSEQ ID NO: 2, in combination with one or more additional cleaningcomposition component.

The choice of additional components is within the skill of the artisanand includes conventional ingredients, including the exemplarynon-limiting components set forth below.

The choice of components may include, for textile care, such as laundry,the consideration of the type of textile to be cleaned, the type and/ordegree of soiling, the temperature at which cleaning is to take place,and the formulation of the detergent product. Although componentsmentioned below are categorized by general header according to aparticular functionality, this is not to be construed as a limitation,as a component may comprise additional functionalities as will beappreciated by the skilled artisan.

Accordingly, the present invention also relates to a composition whichis a cleaning composition.

A composition according to the present invention may further comprise adetergent component, such as a surfactant, a bleach, a dispersantpolymer such as a sulfonated polymer, a complexing agent, a bleachcatalyst such as a manganese bleach catalyst, a crystal growthinhibitor, and/or fabric hueing agents.

In one embodiment, the composition is a phosphate free composition.

The detergent composition of the invention may for example be directedto an ADW (Automatic Dish Wash) composition comprising an enzyme of thepresent invention in combination with one or more additional ADWcomposition components. The choice of additional components is withinthe skill of the artisan and includes conventional ingredients,including the exemplary non-limiting components set forth below.Accordingly, in one aspect, the invention relates to a manual orautomatic dishwashing detergent composition comprising a variant of theinvention, and optionally a surfactant.

The detergent composition of the invention may for example be formulatedas a hand or machine laundry detergent composition including a laundryadditive composition suitable for pre-treatment of stained fabrics and arinse added fabric softener composition, or be formulated as a detergentcomposition for use in general household hard surface cleaningoperations, or be formulated for hand or machine dishwashing operations.Accordingly, in one aspect, the present invention relates to a manual orautomatic laundry detergent composition comprising a variant accordingto the invention.

In a specific aspect, the invention provides a detergentconcentrate/additive comprising the polypeptide of the invention. Thedetergent additive, as well as the detergent composition, may compriseone or more other enzymes such as an amylase, protease, a lipase, aperoxidase, another amylolytic enzyme, e.g., alpha-amylase,glucoamylase, maltogenic amylase, CGTase and/or a cellulase, anothermannanase, pectinase, pectine lyase, cutinase, and/or laccase.

In general the properties of the chosen enzyme(s) should be compatiblewith the selected detergent, (i.e., pH-optimum, compatibility with otherenzymatic and non-enzymatic ingredients, etc.), and the enzyme(s) shouldbe present in effective amounts.

Proteases: Suitable proteases include those of animal, vegetable ormicrobial origin. Microbial origin is preferred. Chemically modified orprotein engineered mutants are included. The protease may be a serineprotease or a metallo protease, preferably an alkaline microbialprotease or a trypsin-like protease. Examples of alkaline proteases aresubtilisins, especially those derived from Bacillus, e.g., subtilisinNovo, subtilisin Carlsberg, subtilisin 309, subtilisin 147 andsubtilisin 168 (described in WO 89/06279). Examples of trypsin-likepro-teases are trypsin (e.g., of porcine or bovine origin) and theFusarium protease described in WO 89/06270 and WO 94/25583.

Examples of useful proteases are the variants described in WO 92/19729,WO 98/20115, WO 98/20116, and WO 98/34946, especially the variants withsubstitutions in one or more of the following positions: 27, 36, 57, 76,87, 97, 101, 104, 120, 123, 167, 170, 194, 206, 218, 222, 224, 235 and274. Preferred commercially available protease enzymes includeALCALASE®, SAVINASE® (SEQ ID NO: 3), PRIMASE®, DURALASE®, ESPERASE®, andKANNASE® (from Novozymes A/S), MAXATASE®, MAXACAL, MAXAPEM®, PROPERASE®,PURAFECT®, PURAFECT OXP®, FN2®, FN3®, FN4® (Genencor InternationalInc.).

Lipases: Suitable lipases include those of bacterial or fungal origin.Chemically modified or protein engineered mutants are included. Examplesof useful lipases include lipases from Humicola (synonym Thermomyces),e.g., from H. lanuginosa (T. lanuginosus) as described in EP 258 068 andEP 305 216 or from H. insolens as described in WO 96/13580, aPseudomonas lipase, e.g., from P. alcaligenes or P. pseudoalcaligenes(EP 218 272), P. cepacia (EP 331 376), P. stutzeri (GB 1,372,034), P.fluorescens, Pseudomonas sp. strain SD 705 (WO 95/06720 and WO96/27002), P. wisconsinensis (WO 96/12012), a Bacillus lipase, e.g.,from B. subtilis (Dartois et al. (1993), Biochemica et Biophysica Acta,1131:253-360), B. stearothermophilus (JP 64/744992) or B. pumilus (WO91/16422). Other examples are lipase variants such as those described inWO 92/05249, WO 94/01541, EP 407 225, EP 260 105, WO 95/35381, WO96/00292, WO 95/30744, WO 94/25578, WO 95/14783, WO 95/22615, WO97/04079 and WO 97/07202.

Preferred commercially available lipase enzymes include LIPOLASE<™> andLIPOLASE ULTRA<™> (Novozymes A/S).

Amylases: Suitable amylases (alpha and/or beta) include those ofbacterial or fungal origin. Chemically modified or protein engineeredmutants are included. Amylases include, for example, alpha-amylasesobtained from Bacillus, e.g., a special strain of B. licheniformis,described in more detail in GB 1,296,839. Examples of usefulalpha-amylases are the variants described in WO 94/02597, WO 94/18314,WO 96/23873, and WO 97/43424, especially the variants with substitutionsin one or more of the following positions: 15, 23, 105, 106, 124, 128,133, 154, 156, 181, 188, 190, 197, 202, 208, 209, 243, 264, 304, 305,391, 408, and 444. Commercially available alpha-amylases are DURAMYL<™>,LIQUEZYME™, TERMAMYL<™>, NATALASE<™>, FUNGAMYL<™> and BAN<™> (NovozymesA/S), Preferenz S100, Preferenz S110, Preferenz S1000 (SEQ ID NO: 11),Excellenz S110, Excellenz S1000, Excellenz S2000, RAPIDASE<™> andPURASTAR<™> (from Genencor International Inc.).

Cellulases: Suitable cellulases include those of bacterial or fungalorigin. Chemically modified or protein engineered mutants are included.Suitable cellulases include cellulases from the genera Bacillus,Pseudomonas, Humicola, Fusarium, Thielavia, Acremonium, e.g., the fungalcellulases produced from Humicola insolens, Myceliophthora thermophilaand Fusarium oxysporum disclosed in U.S. Pat. Nos. 4,435,307, 5,648,263,5,691,178, 5,776,757 and WO 89/09259. Especially suitable cellulases arethe alkaline or neutral cellulases having colour care benefits. Examplesof such cellulases are cellulases described in EP 0 495 257, EP 0 531372, WO 96/11262, WO 96/29397, WO 98/08940. Other examples are cellulasevariants such as those described in WO 94/07998, EP 0 531 315, U.S. Pat.Nos. 5,457,046, 5,686,593, 5,763,254, WO 95/24471, WO 98/12307 andPCT/DK98/00299.

Commercially available cellulases include CELLUZYME®, and CAREZYME®(Novozymes A/S), CLAZINASE®, and PURADAX HA® (Genencor InternationalInc.), and KAC-500(B)® (Kao Corporation).

Peroxidases/Oxidases: Suitable peroxidases/oxidases include those ofplant, bacterial or fungal origin. Chemically modified or proteinengineered mutants are included. Examples of useful peroxidases includeperoxidases from Coprinus, e.g., from C. cinereus, and variants thereofas those described in WO 93/24618, WO 95/10602, and WO 98/15257.Commercially available peroxidases include GUARDZYME® (Novozymes A/S).

Lechinases/Beta-glucanases: Suitable Lechinases include those ofbacterial or fungal origin. They may be chemically modified or proteinengineered. Examples of useful beta-glucanases include those describedin WO 2015/144824 (Novozymes A/S) and WO 99/06516 (Henkel KGAA).

The detergent enzyme(s) may be included in a detergent composition byadding separate additives containing one or more enzymes, or by adding acombined additive comprising all of these enzymes. A detergent additiveof the invention, i.e., a separate additive or a combined additive, canbe formulated, e.g., granulate, a liquid, a slurry, etc. Preferreddetergent additive formulations are granulates, in particularnon-dusting granulates, liquids, in particular stabilized liquids, orslurries.

Non-dusting granulates may be produced, e.g., as disclosed in U.S. Pat.Nos. 4,106,991 and 4,661,452 and may optionally be coated by methodsknown in the art. Examples of waxy coating materials are poly(ethyleneoxide) products (polyethyleneglycol, PEG) with mean molar weights of1000 to 20000; ethoxylated nonyl-phenols having from 16 to 50 ethyleneoxide units; ethoxylated fatty alcohols in which the alcohol containsfrom 12 to 20 carbon atoms and in which there are 15 to 80 ethyleneoxide units; fatty alcohols; fatty acids; and mono- and di- andtriglycerides of fatty acids. Examples of film-forming coating materialssuitable for application by fluid bed techniques are given in GB1483591. Liquid enzyme preparations may, for instance, be stabilized byadding a polyol such as propylene glycol, a sugar or sugar alcohol,lactic acid or boric acid according to established methods. Protectedenzymes may be prepared according to the method disclosed in EP 238 216.

The detergent composition of the invention may be in any convenientform, e.g., a bar, a tablet, a powder, a granule, a paste or a liquid. Aliquid detergent may be aqueous, typically containing up to 70% waterand 0-30% organic solvent, or non-aqueous.

The detergent composition comprises one or more surfactants, which maybe non-ionic including semi-polar and/or anionic and/or cationic and/orzwitterionic. The surfactants are typically present at a level of from0.1% to 60% by weight.

When included therein the detergent will usually comprise from about 1%to about 40% of an anionic surfactant such as linearalkylbenzenesulfonate, alpha-olefinsulfonate, alkyl sulfate (fattyalcohol sulfate), alcohol ethoxysulfate, secondary alkanesulfonate,alpha-sulfo fatty acid methyl ester, alkyl- or alkenylsuccinic acid orsoap.

When included therein the detergent will usually comprise from about0.2% to about 40% of a non-ionic surfactant such as alcohol ethoxylate,nonyl-phenol ethoxylate, alkylpolyglycoside, alkyldimethylamine-oxide,ethoxylated fatty acid monoethanol-amide, fatty acid mono-ethanolamide,polyhydroxy alkyl fatty acid amide, or N-acyl N-alkyl derivatives ofglucosamine (“glucamides”).

The detergent may comprise 0-65% of a detergent builder or complexingagent such as MGDA, GLDA, zeolite, diphosphate, tripho-sphate,phosphonate, carbonate, citrate, nitrilotriacetic acid,ethylenediaminetetraacetic acid, diethylenetriaminepentaacetic acid,alkyl- or alkenylsuccinic acid, soluble silicates or layered silicates(e.g. SKS-6 from Hoechst).

The detergent may comprise one or more polymers. Examples arecarboxymethylcellulose, poly(vinyl-pyrrolidone), poly (ethylene glycol),poly(vinyl alcohol), poly(vinylpyridine-N-oxide), poly(vinylimidazole),polycarboxylates such as sulfonated polymers, polyacrylates,maleic/acrylic acid copolymers and lauryl methacrylate/acrylic acidco-polymers.

The detergent may contain a bleaching system, which may comprise a H₂O₂source such as perborate or percarbonate which may be combined with aperacid-forming bleach activator such as bleach catalysts, e.g. Mn-basedor Co-based, tetraacetylethylenediamine ornonanoyloxyben-zenesul-fonate. Alternatively, the bleaching system maycomprise peroxyacids of, e.g., the amide, imide, or sulfone type.

The enzyme(s) of the detergent composition of the invention may bestabilized using conventional stabilizing agents, e.g., a polyol such aspropylene glycol or glycerol, a sugar or sugar alcohol, lactic acid,boric acid, or a boric acid derivative, e.g., an aromatic borate ester,or a phenyl boronic acid derivative such as 4-formylphenyl boronic acid,and the composition may be formulated as described in, e.g., WO 92/19709and WO 92/19708.

The detergent may also contain other conventional detergent ingredientssuch as e.g. fabric conditioners including clays, foam boosters, sudssuppressors, anti-corrosion agents, soil-suspending agents, anti-soilre-deposition agents, dyes, bactericides, optical brighteners,hydrotropes, tarnish inhibitors, or perfumes.

A hydrotrope is a compound that solubilises hydrophobic compounds inaqueous solutions (or oppositely, polar substances in a non-polarenvironment). Typically, hydrotropes have both hydrophilic and ahydrophobic character (so-called amphiphilic properties as known fromsurfactants); however the molecular structure of hydrotropes generallydo not favor spontaneous self-aggregation, see e.g. review by Hodgdonand Kaler (2007), Current Opinion in Colloid & Interface Science 12:121-128. Hydrotropes do not display a critical concentration above whichself-aggregation occurs as found for surfactants and lipids formingmiceller, lamellar or other well defined meso-phases. Instead, manyhydrotropes show a continuous-type aggregation process where the sizesof aggregates grow as concentration increases. However, many hydrotropesalter the phase behavior, stability, and colloidal properties of systemscontaining substances of polar and non-polar character, includingmixtures of water, oil, surfactants, and polymers. Hydrotropes areclassically used across industries from pharma, personal care, food, totechnical applications. Use of hydrotropes in detergent compositionsallow for example more concentrated formulations of surfactants (as inthe process of compacting liquid detergents by removing water) withoutinducing undesired phenomena such as phase separation or high viscosity.

The detergent composition may comprise about 0-65% by weight, such asabout 5% to about 50% of a detergent builder or co-builder, or a mixturethereof. In a dish wash detergent, the level of builder is typically40-65%, particularly 50-65%. The builder and/or co-builder mayparticularly be a chelating agent that forms water-soluble complexeswith Ca and Mg. Any builder and/or co-builder known in the art for usein laundry/ADW/hard surface cleaning detergents may be utilized.Non-limiting examples of builders include zeolites, diphosphates(pyrophosphates), triphosphates such as sodium triphosphate (STP orSTPP), carbonates such as sodium carbonate, soluble silicates such assodium metasilicate, layered silicates (e.g., SKS-6 from Hoechst),ethanolamines such as 2-aminoethan-1-ol (MEA), diethanolamine (DEA, alsoknown as 2,2′-iminodiethan-1-ol), triethanolamine (TEA, also known as2,2′,2″-nitrilotriethan-1-ol), and (carboxymethyl)inulin (CMI), andcombinations thereof.

The detergent may comprise 0-30% by weight, such as about 1% to about20%, of a bleaching system. Any bleaching system known in the art foruse in laundry/ADW/hard surface cleaning detergents may be utilized.Suitable bleaching system components include bleaching catalysts,photobleaches, bleach activators, sources of hydrogen peroxide such assodium percarbonate, sodium perborates and hydrogen peroxide-urea (1:1),preformed peracids and mixtures thereof. Suitable preformed peracidsinclude, but are not limited to, peroxycarboxylic acids and salts,diperoxydicarboxylic acids, perimidic acids and salts,peroxymonosulfuric acids and salts, for example, Oxone®, and mixturesthereof. Non-limiting examples of bleaching systems includeperoxide-based bleaching systems, which may comprise, for example, aninorganic salt, including alkali metal salts such as sodium salts ofperborate (usually mono- or tetra-hydrate), percarbonate, persulfate,perphosphate, persilicate salts, in combination with a peracid-formingbleach activator. The term bleach activator is meant herein as acompound which reacts with hydrogen peroxide to form a peracid viaperhydrolysis. The peracid thus formed constitutes the activated bleach.Suitable bleach activators to be used herein include those belonging tothe class of esters, amides, imides or anhydrides. Suitable examples aretetraacetylethylenediamine (TAED), sodium4-[(3,5,5-trimethylhexanoyl)oxy]benzene-1-sulfonate (ISONOBS),4-(dodecanoyloxy)benzene-1-sulfonate (LOBS),4-(decanoyloxy)benzene-1-sulfonate, 4-(decanoyloxy)benzoate (DOBS orDOBA), 4-(nonanoyloxy)benzene-1-sulfonate (NOBS), and/or those disclosedin WO98/17767. A particular family of bleach activators of interest wasdisclosed in EP624154 and particulary preferred in that family is acetyltriethyl citrate (ATC). ATC or a short chain triglyceride like triacetinhas the advantage that it is environmentally friendly Furthermore acetyltriethyl citrate and triacetin have good hydrolytical stability in theproduct upon storage and are efficient bleach activators. Finally ATC ismultifunctional, as the citrate released in the perhydrolysis reactionmay function as a builder. Alternatively, the bleaching system maycomprise peroxyacids of, for example, the amide, imide, or sulfone type.The bleaching system may also comprise peracids such as6-(phthalimido)peroxyhexanoic acid (PAP). The bleaching system may alsoinclude a bleach catalyst. In some embodiments the bleach component maybe an organic catalyst selected from the group consisting of organiccatalysts having the following formulae:

(iii) and mixtures thereof;wherein each R¹ is independently a branched alkyl group containing from9 to 24 carbons or linear alkyl group containing from 11 to 24 carbons,preferably each R¹ is independently a branched alkyl group containingfrom 9 to 18 carbons or linear alkyl group containing from 11 to 18carbons, more preferably each R¹ is independently selected from thegroup consisting of 2-propylheptyl, 2-butyloctyl, 2-pentylnonyl,2-hexyldecyl, dodecyl, tetradecyl, hexadecyl, octadecyl, isononyl,isodecyl, isotridecyl and isopentadecyl. Other exemplary bleachingsystems are described, e.g. in WO2007/087258, WO2007/087244,WO2007/087259, EP1867708 (Vitamin K) and WO2007/087242. Suitablephotobleaches may for example be sulfonated zinc or aluminiumphthalocyanines.

Preferably the bleach component comprises a source of peracid inaddition to bleach catalyst, particularly organic bleach catalyst. Thesource of peracid may be selected from (a) pre-formed peracid; (b)percarbonate, perborate or persulfate salt (hydrogen peroxide source)preferably in combination with a bleach activator; and (c) perhydrolaseenzyme and an ester for forming peracid in situ in the presence of waterin a textile or hard surface treatment step.

The detergent may comprise 0-10% by weight, such as 0.5-5%, 2-5%, 0.5-2%or 0.2-1% of a polymer. Any polymer known in the art for use indetergents may be utilized. The polymer may function as a co-builder asmentioned above, or may provide antiredeposition, fiber protection, soilrelease, dye transfer inhibition, grease cleaning and/or anti-foamingproperties. Some polymers may have more than one of the above-mentionedproperties and/or more than one of the below-mentioned motifs. Exemplarypolymers include (carboxymethyl)cellulose (CMC), poly(vinyl alcohol)(PVA), poly(vinylpyrrolidone) (PVP), poly(ethyleneglycol) orpoly(ethylene oxide) (PEG), ethoxylated poly(ethyleneimine),carboxymethyl inulin (CMI), and polycarboxylates such as PAA, PAA/PMA,poly-aspartic acid, and lauryl methacrylate/acrylic acid copolymers,hydrophobically modified CMC (HM-CMC) and silicones, copolymers ofterephthalic acid and oligomeric glycols, copolymers of poly(ethyleneterephthalate) and poly(oxyethene terephthalate) (PET-POET), PVP,poly(vinylimidazole) (PVI), poly(vinylpyridine-N-oxide) (PVPO or PVPNO)and polyvinylpyrrolidone-vinylimidazole (PVPVI). Further exemplarypolymers include sulfonated polycarboxylates, polyethylene oxide andpolypropylene oxide (PEO-PPO) and diquaternium ethoxy sulfate. Otherexemplary polymers are disclosed in, e.g., WO 2006/130575. Salts of theabove-mentioned polymers are also contemplated.

The detergent compositions of the present invention may also comprisefabric hueing agents such as dyes or pigments, which when formulated indetergent compositions can deposit onto a fabric when said fabric iscontacted with a wash liquor comprising said detergent compositions andthus altering the tint of said fabric through absorption/reflection ofvisible light. Fluorescent whitening agents emit at least some visiblelight. In contrast, fabric hueing agents alter the tint of a surface asthey absorb at least a portion of the visible light spectrum. Suitablefabric hueing agents include dyes and dye-clay conjugates, and may alsoinclude pigments. Suitable dyes include small molecule dyes andpolymeric dyes. Suitable small molecule dyes include small molecule dyesselected from the group consisting of dyes falling into the Colour Index(C.I.) classifications of Direct Blue, Direct Red, Direct Violet, AcidBlue, Acid Red, Acid Violet, Basic Blue, Basic Violet and Basic Red, ormixtures thereof, for example as described in WO2005/03274,WO2005/03275, WO2005/03276 and EP1876226 (hereby incorporated byreference). The detergent composition preferably comprises from about0.00003 wt % to about 0.2 wt %, from about 0.00008 wt % to about 0.05 wt%, or even from about 0.0001 wt % to about 0.04 wt % fabric hueingagent. The composition may comprise from 0.0001 wt % to 0.2 wt % fabrichueing agent, this may be especially preferred when the composition isin the form of a unit dose pouch. Suitable hueing agents are alsodisclosed in, e.g. WO 2007/087257 and WO2007/087243.

It is at present contemplated that in the detergent compositions anyenzyme, in particular the alpha amylase polypeptides of the invention,may be added in an amount corresponding to 0.01-100 mg of enzyme proteinper liter of wash liquor, preferably 0.05-5 mg of enzyme protein perliter of wash liquor, in particular 0.1-1 mg of enzyme protein per literof wash liquor.

The alpha amylase polypeptides of the invention may additionally beincorporated in the detergent formulations disclosed in WO 2006/002643,which is hereby incorporated as reference.

Uses

The present invention is also directed to methods for using apolypeptide variant of the invention. The use may be in detergents, inparticular laundry detergent compositions and dishwashing detergentcompositions. Accordingly, the present invention relates to use of avariant comprises at least two substitutions, wherein (a) said firstsubstitution is in an amino acid position selected from the positions260, 288, 294, or 295, and (b) said at least second substitution isselected from any other position in said variant, wherein numbering isaccording to SEQ ID NO: 2, said variant has mannanase activity and hasat least 58%, such as at least 60%, e.g., at least 62%, at least 63%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90%, at least 95%, at least 96%, at least 97%, at least 98%, or atleast 99%, but less than 100% sequence identity to the maturepolypeptide of SEQ ID NO: 1 or the polypeptide of SEQ ID NO: 2.

Thus, the invention provides the use of a polypeptide variant of aparent polypeptide or composition of the invention, in a domestic orindustrial cleaning process. In particular, the invention relates to useof a polypeptide variant according to the invention in laundry,dishwash; such as automatic or manual dishwash, hard surface cleaning,industrial and institutional cleaning, textile desizing, starchmodification, starch liquefaction, saccharification, feed, baking, orbrewing.

In one embodiment, the use is cleaning of fabric, for example laundry.

In another embodiment, the use is cleaning of ceramic, plastic or glassmaterial, for example dishwashing.

Accordingly, the polypeptide variants of the invention are applicable asa component in washing, dishwashing, and hard surface cleaning detergentcompositions (in either a domestic or industrial setting).

The invention described and claimed herein is not to be limited in scopeby the specific aspects herein disclosed, since these aspects areintended as illustrations of several aspects of the invention. Anyequivalent aspects are intended to be within the scope of thisinvention. Indeed, various modifications of the invention in addition tothose shown and described herein will become apparent to those skilledin the art from the foregoing description. Such modifications are alsointended to fall within the scope of the appended claims. In the case ofconflict, the present disclosure including definitions will control.

EXAMPLES Example 1 Site-Saturation Library Generation

The gene of Mannanase (SEQ ID NO: 3) was cloned into the Bacillussubtilis expression cassette and transformed in a derivative of theexpression host, Bacillus subtilis 168, deficient in alkaline protease,neutral protease, alpha-amylase and pectate lyase. Site-saturationlibraries were generated by the method known as “Mega PCR” approach ineach mentioned position in the Mannanase gene with NNS doping in theforward mutagenic primer. NNS is a well-known method, where the “N”designates any of the four nucleotide bases and “S” designates thenulceotides “C” and “G”.

Two PCR reactions were performed, wherein 1) was generation ofC-terminal fragment with the flanking C-terminal reverse primer and theforward mutagenic primer, and 2) was generation of Mega PCR productusing the C-terminal fragment as the reverse mega-primer and theflanking N-terminal forward primer to give the full-length cassette. TheMega PCR product was then transformed in to the Bacillus host, wheresite-specific homologous recombination in the Bacillus chromosome tookplace.

After 18-20 hours of growth in LB agar media with chloramphinecol forantibiotic selection, the transformed colonies were picked andinoculated in to the aqueous growth media, i.e. TB-Gly media. After 3days of growth, culture PCR was carried out by initial heat lysis ofcells, followed by PCR. The sequence of the PCR products were confirmedby sanger sequencing and the resulting variants were tested in screeningassays. The polymerase used for the PCR reaction was Phusion DNApolymerase (obtained from ThermoScientific, Cat. No.: F530L).

Example 2 Variant Generation by Site-Directed Mutagenesis

The gene of Mannanase (SEQ ID NO: 3) was cloned into the Bacillussubtilis expression cassette and transformed in the expression host,Bacillus subtilis as described in Example 1. A Mega PCR-basedsite-directed mutagenesis (SDM) was carried out to generate variants ofthe Mannanase gene by introducing mutations at specific sites (asdescribed in Example 1). SDM was carried out using a single mutagenicprimer of 20-30 base pairs with the desired amino acid change(substitution/deletion/insertion) lying in the middle of theoligonucleotide with sufficient flanking residues (9-15 base pairs). TwoPCR reactions were involved 1) generation of C-terminal fragment withthe flanking C-terminal reverse primer and the forward mutagenic primer2) generation of Mega PCR product using the C-terminal fragment as thereverse mega-primer and the flanking N-terminal forward primer to givethe full-length cassette. The Mega PCR product was then transformed into the Bacillus host, where site-specific homologous recombination inthe Bacillus chromosome takes place.

After 18-20 hours of growth in LB agar media with appropriateantibiotic, the transformed colonies were picked and inoculated in tothe aqueous expression media and given for screening assays. The hitsfrom the screening assays were subjected to culture PCR and sent forsequence confirmation. The polymerase used for the PCR reaction wasPhusion DNA polymerase (obtained from ThermoScientific, Cat. No.:F530L).

Example 3 Detergent Stability Determination

Variants of the present invention and generated as described in Example1 and 2, were tested for detergent stability at pH 9.0 and pH 10.5-10.8.Stability test was performed by incubating the variants in detergent fordifferent length of time and temperature (given in the tables below)depending on the stability of wild-type (WT) or backbone and comparingthe activity against control plate which was incubated at 4° C. for thesame duration. The stability test was performed in two differentdetergents (Model O detergent described in Table 1, and commerciallyavailable detergent Arms & Hammer (listed as A&H)).

To the Model O detergent was added a protease, and for the A&H detergenta protease and protease inhibitor are already present in the detergent.

The residual activity was measured by using the Mannanase enzyme assayusing insoluble Azo-carob-galactomannan substrate from Megazyme.Substrate was incubated with enzyme for 20 min at 25° C. for 20 min,shaking at 800 rpm. The reaction mixture was kept static for 10 min toallow insoluble substrate to settle. Enzyme activity was measured byreading the optical density of supernatant at 590 nm. The residualactivity was calculated by taking the ratio of Stress response toUn-stress response and expressing in terms of % RA.

TABLE 1 Model O detergent Compound Content of compound (% w/w) Na-LAS(linear alkylbenzene sulphonate) 5.3 AEOS (Alkylethoxy sulphate) 10.7Soyfatty acid 1.0 AEO (Alcohol polyethoxylated) 5.3 TEA (Trietanolamine)0.4 Sodium citrate 2.0 CaCl₂ 0.02 Water 75.3Water hardness adjusted to 12° dH by addition of CaCl₂, MgCl₂, andNaHCO₃ (Ca²⁺:Mg²⁺:HCO³⁻=2:1:4.5) to the test system. After washing thetextiles were flushed in tap water and dried.

Table 2 and Table 3 below show the stability results obtained fromExample 3.

TABLE 2 Variants of the present invention having an improved half lifeImprovement Factor (HIF) measured as improved stability compared to theparent mannanase (SEQ ID NO: 1) % Residual Substitutions introduced inSEQ ID NO: 1 pH Detergent Temperature Time Activity HIF S3P G47S E77TY93Q K116R A136P G257W L288I L294P S295K 9 Model O 40 C. 24 hr 81.2 3.0S3P G47S E77T Y93Q K116R A136P W260F L288I L294P S295K 9 Model O 40 C.24 hr 83.7 10.9 W260F L288I L294P S295L 9 Model O 40 C. 24 hr 88.4 16.9W260F L288I L294P S295V 9 Model O 40 C. 24 hr 86.1 13.5 W260F L288IL294P S295P 9 Model O 40 C. 24 hr 83.7 11.4 L288I L294P S295V 9 Model O40 C. 24 hr 80.1 6.2 L288I L294P S295K 9 Model O 40 C. 24 hr 77.5 7.1L288I L294P S295L 9 Model O 40 C. 24 hr 76.0 5.9 L288I L294P S295K G47A9 Model O 45 C. 16 hr 59.6 6.3 L288I L294P S295K K116R 9 Model O 45 C.16 hr 53.0 4.6 L288I L294P S295K G47S 9 Model O 45 C. 16 hr 53.8 5.1L288I L294P S295K Y93Q 9 Model O 45 C. 16 hr 66.7 7.5 L288I L294P S295KT37P 9 Model O 45 C. 16 hr 53.9 4.6 L288I L294P S295K A136P 9 Model O 45C. 16 hr 69.3 8.1 W260F L288I L294P S295V G47A 9 Model O 45 C. 16 hr90.4 38.8 W260F L288I L294P S295V G47S 9 Model O 45 C. 16 hr 87.8 28.9W260F L288I L294P S295V K116R 9 Model O 45 C. 16 hr 87.6 40.9 W260FL288I L294P S295V Y93Q 9 Model O 45 C. 16 hr 80.2 16.4 W260F L288I L294PS295V T37P 9 Model O 45 C. 16 hr 82.5 14.6 W260F L288I L294P S295V E77T9 Model O 45 C. 16 hr 75.6 9.7 W260F L288I L294P S295V A136P 9 Model O45 C. 16 hr 87.9 23.8 L288I L294P S295P 9 Model O 45 C. 16 hr 63.3 7.2S3P G47S Y93Q K116R A136P W260F L288I L294P S295K 9 Model O 50 C. 16 hr60.3 13.8 S3P G47S E77T K116R A136P W260F L288I L294P S295K 9 Model O 50C. 16 hr 35.7 6.6 S3P G47S E77T Y93Q A136P W260F L288I L294P S295K 9Model O 50 C. 16 hr 52.5 10.5 S3P G47S E77T Y93Q K116R A136P L288I L294PS295K 9 Model O 50 C. 16 hr 28.2 5.3 W260F L288I L294P S295V Y93A 9Model O 50 C. 24 hr 73.4 36.1 W260F L288I L294P S295V Y93I 9 Model O 50C. 24 hr 73.8 36.1 W260F L288I L294P S295V Y93F 9 Model O 50 C. 24 hr68.7 30.1 W260F L288I L294P S295V Y93R 9 Model O 50 C. 24 hr 66.1 31.5W260F L288I L294P S295V A83P 9 Model O 50 C. 24 hr 63.6 22.0 W260F L288IL294P S295V V82I 9 Model O 50 C. 24 hr 63.3 26.6 W260F L288I L294P S295VL81R 9 Model O 50 C. 24 hr 37.1 10.9 W260F L288I L294P S295V E77N 9Model O 50 C. 24 hr 57.1 19.7 W260F L288I L294P S295V A83S 9 Model O 50C. 24 hr 57.1 21.3 W260F L288I L294P S295V S202R 9 Model O 50 C. 24 hr82.5 36.1 W260F L288I L294P S295V G47K 9 Model O 50 C. 24 hr 53.4 17.8W260F L288I L294P S295V G47T 9 Model O 50 C. 24 hr 61.8 24.7 W260F L288IL294P S295V H80K 9 Model O 50 C. 24 hr 58.8 20.6 W260F L288I L294P S295VD135P 9 Model O 50 C. 24 hr 58.4 18.0 W260F L288I L294P S295V I96A 9Model O 50 C. 24 hr 20.2 6.8 W260L L288I L294P S295V 9 Model O 50 C. 24hr 65.6 21.3 W260F L288I L294R S295V 9 Model O 50 C. 24 hr 51.9 16.4W260F L288I L294P S295V 9 Model O 50 C. 24 hr 54.1 16.0 W260F L288IL294P S295V G47R 9 Model O 50 C. 40 hr 34.6 16.6 W260F L288I L294K S295V9 Model O 50 C. 40 hr 23.0 12.1 W260F L288I L294P S295V G47Y 9 Model O50 C. 40 hr 25.8 13.2 W260F L288I L294P S295V H80R 9 Model O 50 C. 40 hr34.3 15.8 W260F L288I L294P S295V D118K 9 Model O 50 C. 40 hr 28.2 13.7W260F L288I L294P S295V T119R 9 Model O 50 C. 40 hr 27.3 12.7 W260FL288I L294P S295V S202E 9 Model O 50 C. 40 hr 59.6 31.5 W260F L288IL294P S295V G257E 9 Model O 50 C. 40 hr 36.7 16.4 W260F L288I L294PS295V A136P D14A 9 Model O 50 C. 40 hr 22.2 11.6 W260F L288I L294P S295VA136P T37P 9 Model O 50 C. 40 hr 55.5 27.6 W260F L288I L294P S295V A136PG47A 9 Model O 50 C. 40 hr 54.9 29.8 W260F L288I L294P S295V A136P G47K9 Model O 50 C. 40 hr 46.6 23.4 W260F L288I L294P S295V A136P G47R 9Model O 50 C. 40 hr 44.8 21.5 W260F L288I L294P S295V A136P G47S 9 ModelO 50 C. 40 hr 51.8 27.1 W260F L288I L294P S295V A136P G47Y 9 Model O 50C. 40 hr 40.9 19.6 W260F L288I L294P S295V A136P E77T 9 Model O 50 C. 40hr 47.3 26.0 W260F L288I L294P S295V A136P H80R 9 Model O 50 C. 40 hr59.4 29.9 W260F L288I L294P S295V A136P L81R 9 Model O 50 C. 40 hr 60.635.6 W260F L288I L294P S295V A136P V82I 9 Model O 50 C. 40 hr 57.7 31.5W260F L288I L294P S295V A136P A83P 9 Model O 50 C. 40 hr 49.7 23.4 W260FL288I L294P S295V A136P A83S 9 Model O 50 C. 40 hr 52.4 26.7 W260F L288IL294P S295V A136P Y93A 9 Model O 50 C. 40 hr 48.1 23.2 W260F L288I L294PS295V A136P Y93Q 9 Model O 50 C. 40 hr 60.6 36.7 W260F L288I L294P S295VA136P K116R 9 Model O 50 C. 40 hr 54.6 26.7 W260F L288I L294P S295VA136P D118K 9 Model O 50 C. 40 hr 57.8 31.6 W260F L288I L294P S295VA136P T119R 9 Model O 50 C. 40 hr 58.9 15.5 W260F L288I L294P S295VA136P 9 Model O 50 C. 40 hr 51.7 26.9 W260F L288I L294P S295V A136PS202E 9 Model O 50 C. 40 hr 52.2 26.3 W260F L288I L294P S295V A136PS202R 9 Model O 50 C. 40 hr 74.7 59.3 W260F L288I L294P S295V A136PG257E 9 Model O 50 C. 40 hr 56.9 32.1 S3P G47S E77T Y93Q K116R A136PW260F L288I L294P S295V 9 Model O 50 C. 40 hr 52.9 23.8 W260F L288IL294P S295V S202R S8T 9 Model O 50 C. 65 hr 48.7 37.7 W260F L288I L294PS295V S202R T37P 9 Model O 50 C. 65 hr 40.2 27.5 W260F L288I L294P S295VS202R E41V 9 Model O 50 C. 65 hr 55.5 37.3 W260F L288I L294P S295V S202RG47A 9 Model O 50 C. 65 hr 38.3 28.6 W260F L288I L294P S295V S202R G47K9 Model O 50 C. 65 hr 33.7 24.6 W260F L288I L294P S295V S202R G47R 9Model O 50 C. 65 hr 33.7 24.1 W260F L288I L294P S295V S202R G47S 9 ModelO 50 C. 65 hr 34.5 25.0 W260F L288I L294P S295V S202R G47Y 9 Model O 50C. 65 hr 27.0 20.6 W260F L288I L294P S295V S202R E77T 9 Model O 50 C. 65hr 38.6 28.6 W260F L288I L294P S295V S202R D78G 9 Model O 50 C. 65 hr42.7 29.9 W260F L288I L294P S295V S202R H80K 9 Model O 50 C. 65 hr 44.633.0 W260F L288I L294P S295V S202R A83P 9 Model O 50 C. 65 hr 35.0 25.8W260F L288I L294P S295V S202R A83S 9 Model O 50 C. 65 hr 35.4 25.5 W260FL288I L294P S295V S202R Y93A 9 Model O 50 C. 65 hr 41.0 28.5 W260F L288IL294P S295V S202R Y93Q 9 Model O 50 C. 65 hr 57.8 47.6 W260F L288I L294PS295V S202R S98P 9 Model O 50 C. 65 hr 49.4 38.6 W260F L288I L294P S295VS202R K116R 9 Model O 50 C. 65 hr 33.9 25.1 W260F L288I L294P S295VS202R D118K 9 Model O 50 C. 65 hr 39.9 28.8 W260F L288I L294P S295VS202R T119R 9 Model O 50 C. 65 hr 41.3 31.1 W260F L288I L294P S295VS202R A136P 9 Model O 50 C. 65 hr 55.5 45.1 W260F L288I L294P S295VS202R 9 Model O 50 C. 65 hr 43.2 30.8 W260F L288I L294P S295V S202RG257E 9 Model O 50 C. 65 hr 48.9 37.4 W260F L288I L294P S295V S202RT299P 9 Model O 50 C. 65 hr 38.6 28.3 W260L L288I L294P S295V S202R 9Model O 50 C. 65 hr 62.4 51.2 S8T A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 73.9 90.7 D14A A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 20.0 17.3 D14S A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 39.6 30.2 T37P A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 60.5 54.9 E41V A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 66.0 64.6 G47A A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 59.4 52.2 G47K A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 64.1 62.9 G47R A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 58.8 51.1 G47S A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 60.9 51.7 G47Y A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 55.8 45.3 E77N A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 63.6 54.3 E77T A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 60.8 55.3 D78G A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 66.8 70.6 H80K A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 67.0 69.1 H80R A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 66.1 67.7 L81R A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 36.6 27.3 V82I A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 68.5 79.1 A83P A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 61.5 54.1 A83S A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 62.6 58.2 A83T A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 54.1 44.7 Y93A A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 59.9 53.7 Y93F A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 66.0 63.6 Y93I A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 65.7 62.9 Y93Q A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 73.9 96.4 Y93R A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 62.7 54.9 S98P A136P S202R W260F L288I L294P S295V 9Model O 50 C. 65 hr 73.3 85.6 K116R A136P S202R W260F L288I L294P S295V9 Model O 50 C. 65 hr 63.9 61.0 D118K A136P S202R W260F L288I L294PS295V 9 Model O 50 C. 65 hr 67.2 68.5 T119R A136P S202R W260F L288IL294P S295V 9 Model O 50 C. 65 hr 64.1 66.1 A136P S202R G257A W260FL288I L294P S295V 9 Model O 50 C. 65 hr 67.9 69.6 A136P S202R G257EW260F L288I L294P S295V 9 Model O 50 C. 65 hr 71.0 80.5 A136P S202RW260L L288I L294P S295V 9 Model O 50 C. 65 hr 79.0 96.4 A136P S202RW260F L288I L294P S295V T299P 9 Model O 50 C. 65 hr 62.9 60.8 S3P A136PS202R W260F L288I L294P S295V 9 Model O 50 C. 65 hr 68.6 89.7 A136PS202R W260F L288I L294P S295I 9 Model O 50 C. 65 hr 51.6 42.0 A136PS202R W260F L288I L294P S295P 9 Model O 50 C. 65 hr 46.7 35.2 G47Q A136PS202R W260F L288I L294P S295V 9 Model O 50 C. 65 hr 65.6 59.8 G47T A136PS202R W260F L288I L294P S295V 9 Model O 50 C. 65 hr 63.6 65.2 A136PS202R W260F L288I L294P S295V 9 Model O 50 C. 114 hr 45.1 62.2 E41V Y93FS202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 24.5 42.6 E41V Y93IS202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 28.3 41.0 E41V Y93QS202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 30.8 50.8 E41V Y93RS202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 22.5 36.2 E41V S98PS202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 29.8 49.5 E41VD118K S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 23.2 37.0E41V T119R S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 27.742.1 E41V S202R G257E W260F L288I L294P S295V 9 Model O 50 C. 138 hr25.8 45.2 S8T Y93Q S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr36.4 58.2 G47A Y93Q S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr21.0 36.6 G47K Y93Q S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr24.4 41.3 G47Q Y93Q S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr33.7 53.5 G47R Y93Q S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr23.6 41.6 G47S Y93Q S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr25.7 42.5 G47T Y93Q S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr28.3 46.1 E77N Y93Q S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr29.3 47.7 E77T Y93Q S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr25.7 44.1 D78G Y93Q S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr29.6 49.9 H80K Y93Q S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr28.0 48.1 H80R Y93Q S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr31.6 51.2 A83T Y93Q S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr21.2 37.6 Y93Q S98P S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr35.5 59.3 Y93Q K116R S202R W260F L288I L294P S295V 9 Model O 50 C. 138hr 27.0 46.2 Y93Q D118K S202R W260F L288I L294P S295V 9 Model O 50 C.138 hr 30.3 50.4 Y93Q T119R S202R W260F L288I L294P S295V 9 Model O 50C. 138 hr 28.6 49.8 Y93Q S202R G257E W260F L288I L294P S295V 9 Model O50 C. 138 hr 32.3 53.1 T37P G47K A136P S202R W260F L288I L294P S295V 9Model O 50 C. 138 hr 30.0 49.1 G47K E77N A136P S202R W260F L288I L294PS295V 9 Model O 50 C. 138 hr 28.4 47.7 G47K E77T A136P S202R W260F L288IL294P S295V 9 Model O 50 C. 138 hr 25.4 42.7 G47K H80R A136P S202R W260FL288I L294P S295V 9 Model O 50 C. 138 hr 34.1 54.7 G47K V82I A136P S202RW260F L288I L294P S295V 9 Model O 50 C. 138 hr 34.5 56.6 G47K A83S A136PS202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 30.9 51.3 G47K Y93QA136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 41.6 66.9G47K D118K A136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr30.6 48.1 G47K T119R A136P S202R W260F L288I L294P S295V 9 Model O 50 C.138 hr 28.6 46.9 G47K A136P S202R G257A W260F L288I L294P S295V 9 ModelO 50 C. 138 hr 34.5 56.5 G47K A136P S202R G257E W260F L288I L294P S295V9 Model O 50 C. 138 hr 36.1 61.2 G47Q E77T A136P S202R W260F L288I L294PS295V 9 Model O 50 C. 138 hr 30.5 50.2 G47R E77N A136P S202R W260F L288IL294P S295V 9 Model O 50 C. 138 hr 29.5 48.5 G47R H80K A136P S202R W260FL288I L294P S295V 9 Model O 50 C. 138 hr 29.9 53.1 G47R A83S A136P S202RW260F L288I L294P S295V 9 Model O 50 C. 138 hr 24.9 43.7 G47R A136PS202R G257A W260F L288I L294P S295V 9 Model O 50 C. 138 hr 30.0 49.6G47S H80R A136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr32.7 53.6 G47T E77T A136P S202R W260F L288I L294P S295V 9 Model O 50 C.138 hr 29.0 48.3 G47Y E77T A136P S202R W260F L288I L294P S295V 9 Model O50 C. 138 hr 20.2 37.8 G47Y S98P A136P S202R W260F L288I L294P S295V 9Model O 50 C. 138 hr 27.6 44.6 G47Y T119R A136P S202R W260F L288I L294PS295V 9 Model O 50 C. 138 hr 21.7 40.3 L81R S98P A136P S202R W260F L288IL294P S295V 9 Model O 50 C. 138 hr 20.0 36.2 L81R A136P S202R G257EW260F L288I L294P S295V 9 Model O 50 C. 138 hr 26.6 43.8 V82I Y93Q S202RW260F L288I L294P S295V 9 Model O 50 C. 138 hr 36.8 58.1 A83P Y93Q S202RW260F L288I L294P S295V 9 Model O 50 C. 138 hr 21.5 39.8 A83S Y93Q S202RW260F L288I L294P S295V 9 Model O 50 C. 138 hr 21.6 38.4 Y93Q S202RG257A W260F L288I L294P S295V 9 Model O 50 C. 138 hr 26.7 42.8 G47K H80KA136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 27.0 47.4G47K A83T A136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr23.5 40.4 G47K S98P A136P S202R W260F L288I L294P S295V 9 Model O 50 C.138 hr 35.6 57.3 G47K K116R A136P S202R W260F L288I L294P S295V 9 ModelO 50 C. 138 hr 21.8 36.4 G47K A136P S202R W260F L288I L294P S295V T299P9 Model O 50 C. 138 hr 21.1 38.5 G47R H80R A136P S202R W260F L288I L294PS295V 9 Model O 50 C. 138 hr 35.9 58.9 G47R S98P A136P S202R W260F L288IL294P S295V 9 Model O 50 C. 138 hr 29.3 47.5 G47R A136P S202R G257EW260F L288I L294P S295V 9 Model O 50 C. 138 hr 31.6 49.7 G47S T119RA136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 20.8 36.3 S8TY93Q A136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 27.448.6 T37P Y93Q A136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138hr 33.2 50.5 A83P Y93Q A136P S202R W260F L288I L294P S295V 9 Model O 50C. 138 hr 31.7 52.0 A83T Y93Q A136P S202R W260F L288I L294P S295V 9Model O 50 C. 138 hr 28.8 48.2 Y93Q K116R A136P S202R W260F L288I L294PS295V 9 Model O 50 C. 138 hr 27.3 46.3 Y93Q D118K A136P S202R W260FL288I L294P S295V 9 Model O 50 C. 138 hr 47.6 77.9 G47A A136P S202RW260L L288I L294P S295V 9 Model O 50 C. 138 hr 48.8 86.8 A136P S202RG257E W260L L288I L294P S295V 9 Model O 50 C. 138 hr 41.0 76.5 S8T E41VA136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 30.3 46.2 S8TG47K A136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 28.243.5 S8T G47Q A136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr26.3 44.9 S8T E77T A136P S202R W260F L288I L294P S295V 9 Model O 50 C.138 hr 22.9 40.7 S8T D78G A136P S202R W260F L288I L294P S295V 9 Model O50 C. 138 hr 30.8 55.0 S8T V82I A136P S202R W260F L288I L294P S295V 9Model O 50 C. 138 hr 33.0 53.1 S8T Y93A A136P S202R W260F L288I L294PS295V 9 Model O 50 C. 138 hr 33.0 54.8 S8T T119R A136P S202R W260F L288IL294P S295V 9 Model O 50 C. 138 hr 29.9 50.7 S8T A136P S202R G257E W260FL288I L294P S295V 9 Model O 50 C. 138 hr 39.5 65.5 S3P D78G A136P S202RW260F L288I L294P S295V 9 Model O 50 C. 138 hr 25.7 43.9 S3P Y93I A136PS202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 29.5 47.9 S3P T119RA136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 29.6 49.4 S3PA136P S202R G257E W260F L288I L294P S295V 9 Model O 50 C. 138 hr 33.856.3 G47Q S98P A136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138hr 35.1 57.2 E77N S98P A136P S202R W260F L288I L294P S295V 9 Model O 50C. 138 hr 31.1 53.4 E77T S98P A136P S202R W260F L288I L294P S295V 9Model O 50 C. 138 hr 29.8 49.5 D78G S98P A136P S202R W260F L288I L294PS295V 9 Model O 50 C. 138 hr 31.8 52.7 H80K S98P A136P S202R W260F L288IL294P S295V 9 Model O 50 C. 138 hr 47.2 82.4 Y93A S98P A136P S202R W260FL288I L294P S295V 9 Model O 50 C. 138 hr 23.7 40.7 Y93F S98P A136P S202RW260F L288I L294P S295V 9 Model O 50 C. 138 hr 38.2 64.4 S98P K116RA136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 37.4 62.2S98P A136P S202R G257A W260F L288I L294P S295V 9 Model O 50 C. 138 hr48.9 87.7 S98P A136P S202R G257E W260F L288I L294P S295V 9 Model O 50 C.138 hr 40.9 63.5 E41V A136P S202R G257E W260F L288I L294P S295V 9 ModelO 50 C. 138 hr 40.9 68.8 G47Q A136P S202R G257E W260F L288I L294P S295V9 Model O 50 C. 138 hr 35.9 58.0 G47T A136P S202R G257E W260F L288IL294P S295V 9 Model O 50 C. 138 hr 32.4 53.3 Y93A A136P S202R G257EW260F L288I L294P S295V 9 Model O 50 C. 138 hr 33.5 52.8 K116R A136PS202R G257E W260F L288I L294P S295V 9 Model O 50 C. 138 hr 37.3 69.4D118K A136P S202R G257E W260F L288I L294P S295V 9 Model O 50 C. 138 hr41.8 67.3 T119R A136P S202R G257E W260F L288I L294P S295V 9 Model O 50C. 138 hr 46.6 70.5 E41V V82I A136P S202R W260F L288I L294P S295V 9Model O 50 C. 138 hr 33.9 53.1 G47A V82I A136P S202R W260F L288I L294PS295V 9 Model O 50 C. 138 hr 27.4 45.3 G47R V82I A136P S202R W260F L288IL294P S295V 9 Model O 50 C. 138 hr 27.7 46.6 G47S V82I A136P S202R W260FL288I L294P S295V 9 Model O 50 C. 138 hr 38.0 59.0 G47Y V82I A136P S202RW260F L288I L294P S295V 9 Model O 50 C. 138 hr 21.4 36.9 E77T V82I A136PS202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 34.9 54.5 H80R V82IA136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr 38.1 58.6V82I Y93I A136P S202R W260F L288I L294P S295V 9 Model O 50 C. 138 hr31.7 54.6 V82I K116R A136P S202R W260F L288I L294P S295V 9 Model O 50 C.138 hr 27.8 43.7 Y93Q S202E W260F L288I L294P S295V 9 Model O 50 C. 138hr 23.4 41.0 S98P S202E W260F L288I L294P S295V 9 Model O 50 C. 138 hr27.0 48.2 G47R Y93Q A136P S202R W260F L288I L294P S295V 10.5 A & H 40 C.65 hr 25.6 84.4 G47S Y93Q A136P S202R W260F L288I L294P S295V 10.5 A & H40 C. 65 hr 43.7 91.0 G47Y Y93Q A136P S202R W260F L288I L294P S295V 10.5A & H 40 C. 65 hr 27.7 60.6 D78G Y93Q A136P S202R W260F L288I L294PS295V 10.5 A & H 40 C. 65 hr 49.7 110.5 H80K Y93Q A136P S202R W260FL288I L294P S295V 10.5 A & H 40 C. 65 hr 59.0 141.8 H80R Y93Q A136PS202R W260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 53.0 125.2 A83SY93Q A136P S202R W260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 43.798.1 Y93Q S98P A136P S202R W260F L288I L294P S295V 10.5 A & H 40 C. 65hr 47.3 100.6 Y93Q T119R A136P S202R W260F L288I L294P S295V 10.5 A & H40 C. 65 hr 49.4 117.4 Y93I A136P S202R W260L L288I L294P S295V 10.5 A &H 40 C. 65 hr 32.3 70.4 S8T A136P S202R G257A W260F L288I L294P S295V10.5 A & H 40 C. 65 hr 20.1 47.7 S3P S98P A136P S202R W260F L288I L294PS295V 10.5 A & H 40 C. 65 hr 30.0 63.8 E41V S98P A136P S202R W260F L288IL294P S295V 10.5 A & H 40 C. 65 hr 33.4 71.0 G47A S98P A136P S202R W260FL288I L294P S295V 10.5 A & H 40 C. 65 hr 28.3 63.7 G47S S98P A136P S202RW260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 27.9 64.4 A83S S98P A136PS202R W260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 36.0 80.0 S98PD118K A136P S202R W260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 40.579.7 S98P T119R A136P S202R W260F L288I L294P S295V 10.5 A & H 40 C. 65hr 26.8 60.8 T37P A136P S202R G257E W260F L288I L294P S295V 10.5 A & H40 C. 65 hr 25.9 61.0 G47A A136P S202R G257E W260F L288I L294P S295V10.5 A & H 40 C. 65 hr 24.9 58.3 G47Y A136P S202R G257E W260F L288IL294P S295V 10.5 A & H 40 C. 65 hr 22.3 45.1 E77N A136P S202R G257EW260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 29.5 60.2 A83S A136PS202R G257E W260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 20.4 68.7V82I Y93F A136P S202R W260F L288I L294P S295V 10.5 A & H 40 C. 65 hr24.2 55.7 V82I Y93R A136P S202R W260F L288I L294P S295V 10.5 A & H 40 C.65 hr 20.4 49.3 Y93Q S95D A136P S202R W260F L288I L294P S295V 10.5 A & H40 C. 65 hr 55.2 104.1 Y93Q A97R A136P S202R W260F L288I L294P S295V10.5 A & H 40 C. 65 hr 24.3 54.1 Y93Q A97S A136P S202R W260F L288I L294PS295V 10.5 A & H 40 C. 65 hr 36.3 72.2 Y93Q D104A A136P S202R W260FL288I L294P S295V 10.5 A & H 40 C. 65 hr 39.8 86.8 Y93Q D104G A136PS202R W260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 35.6 66.8 Y93QD104Q A136P S202R W260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 25.156.5 Y93Q S111A A136P S202R W260F L288I L294P S295V 10.5 A & H 40 C. 65hr 47.2 95.2 Y93Q S111K A136P S202R W260F L288I L294P S295V 10.5 A & H40 C. 65 hr 41.0 89.7 Y93Q S111R A136P S202R W260F L288I L294P S295V10.5 A & H 40 C. 65 hr 38.7 83.6 Y93Q I114Q A136P S202R W260F L288IL294P S295V 10.5 A & H 40 C. 65 hr 45.5 97.8 Y93Q I114W A136P S202RW260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 28.7 81.3 Y93Q A136PD139A S202R W260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 67.2 188.0Y93Q A136P D139G S202R W260F L288I L294P S295V 10.5 A & H 40 C. 65 hr30.7 69.8 Y93Q A136P D139R S202R W260F L288I L294P S295V 10.5 A & H 40C. 65 hr 60.7 147.1 Y93Q A136P K142M S202R W260F L288I L294P S295V 10.5A & H 40 C. 65 hr 38.5 85.8 Y93Q A136P K142S S202R W260F L288I L294PS295V 10.5 A & H 40 C. 65 hr 20.0 46.5 Y93Q A136P K142V S202R W260FL288I L294P S295V 10.5 A & H 40 C. 65 hr 37.4 75.9 S8T A136P D139A S202RW260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 25.1 57.2 S8T A136P D139RS202R W260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 41.7 95.8 S3P A136PD139A S202R W260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 20.6 47.0 S3PA136P D139R S202R W260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 26.759.2 S95D S98P A136P S202R W260F L288I L294P S295V 10.5 A & H 40 C. 65hr 42.7 93.0 S98P S111A A136P S202R W260F L288I L294P S295V 10.5 A & H40 C. 65 hr 27.9 66.8 S98P I114M A136P S202R W260F L288I L294P S295V10.5 A & H 40 C. 65 hr 27.1 57.4 S98P I114W A136P S202R W260F L288IL294P S295V 10.5 A & H 40 C. 65 hr 21.6 49.9 S98P A136P D139A S202RW260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 43.6 88.3 S98P A136PD139R S202R W260F L288I L294P S295V 10.5 A & H 40 C. 65 hr 50.4 95.4S98P A136P D139V S202R W260F L288I L294P S295V 10.5 A & H 40 C. 65 hr28.6 62.8 S98P A136P D139W S202R W260F L288I L294P S295V 10.5 A & H 40C. 65 hr 22.4 55.2 S98P A136P K142M S202R W260F L288I L294P S295V 10.5 A& H 40 C. 65 hr 25.4 55.9 E41V Y93Q A136P S202R W260F L288I L294P S295V10.5 A & H 42C 16 hr 51.4 171.4 G47A Y93Q A136P S202R W260F L288I L294PS295V 10.5 A & H 42 C. 16 hr 30.3 91.4 G47Q Y93Q A136P S202R W260F L288IL294P S295V 10.5 A & H 42 C. 16 hr 44.2 129.2 G47T Y93Q A136P S202RW260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 41.8 118.6 E77T Y93QA136P S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 34.2 99.2Y93Q A136P S202R G257A W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr32.7 96.3 Y93Q A136P S202R G257E W260F L288I L294P S295V 10.5 A & H 42C. 16 hr 59.1 194.5 T37R Y93Q A136P S202R W260F L288I L294P S295V 10.5 A& H 42 C. 16 hr 41.3 119.8 R70K Y93Q A136P S202R W260F L288I L294P S295V10.5 A & H 42 C. 16 hr 36.5 106.5 N45G Y93Q A136P S202R W260F L288IL294P S295V 10.5 A & H 42 C. 16 hr 34.5 105.9 Q35L Y93Q A136P S202RW260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 21.8 74.2 N18V Y93Q A136PS202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 43.8 133.8 N18RY93Q A136P S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 38.4114.6 N71S Y93Q A136P S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16hr 28.2 83.9 S74K Y93Q A136P S202R W260F L288I L294P S295V 10.5 A & H 42C. 16 hr 39.1 109.4 Y93Q A136P Y174R S202R W260F L288I L294P S295V 10.5A & H 42 C. 16 hr 23.3 75.3 Y93Q A136P Q143R S202R W260F L288I L294PS295V 10.5 A & H 42 C. 16 hr 27.5 87.5 Y93Q A136P N180R S202R W260FL288I L294P S295V 10.5 A & H 42 C. 16 hr 36.5 105.0 Y93Q A136P Q169AS202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 33.8 99.0 Y93QA136P Q169R S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 30.685.5 Y93Q A136P Q169K S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16hr 30.8 89.6 Y93Q A136P E177S S202R W260F L288I L294P S295V 10.5 A & H42 C. 16 hr 36.1 105.2 Y93Q A136P E177Y S202R W260F L288I L294P S295V10.5 A & H 42 C. 16 hr 33.1 101.1 Y93Q A136P N150T S202R W260F L288IL294P S295V 10.5 A & H 42 C. 16 hr 37.9 110.6 Y93Q A136P N150R S202RW260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 38.0 108.6 Y93Q A136PQ184E S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 34.7 103.1Y93Q A136P Q184K S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr34.6 101.9 Y93Q A136P Q184S S202R W260F L288I L294P S295V 10.5 A & H 42C. 16 hr 28.9 90.3 Y93Q A136P R185G S202R W260F L288I L294P S295V 10.5 A& H 42 C. 16 hr 33.4 99.7 Y93R A136P S202R W260L L288I L294P S295V 10.5A & H 42 C. 16 hr 35.9 107.1 V82I A136P D139A S202R W260F L288I L294PS295V 10.5 A & H 42 C. 16 hr 22.4 74.0 V82I A136P D139R S202R W260FL288I L294P S295V 10.5 A & H 42 C. 16 hr 33.3 96.8 S95D A136P S202RW260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 71.6 380.7 A136P D139AS202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 21.3 70.1 A136PD139R S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 35.9 114.4D65E S98P A136P S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr21.4 69.3 T37R S98P A136P S202R W260F L288I L294P S295V 10.5 A & H 42 C.16 hr 39.0 116.3 R70K S98P A136P S202R W260F L288I L294P S295V 10.5 A &H 42 C. 16 hr 39.1 114.7 N45G S98P A136P S202R W260F L288I L294P S295V10.5 A & H 42 C. 16 hr 29.8 93.4 N71S S98P A136P S202R W260F L288I L294PS295V 10.5 A & H 42 C. 16 hr 26.0 83.7 S74K S98P A136P S202R W260F L288IL294P S295V 10.5 A & H 42 C. 16 hr 40.1 118.0 S98P A136P Y174R S202RW260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 21.9 73.8 S98P A136PY174L S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 26.6 89.4S98P A136P Q143R S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr20.9 66.9 S98P A136P N180R S202R W260F L288I L294P S295V 10.5 A & H 42C. 16 hr 37.8 113.1 S98P A136P Q169A S202R W260F L288I L294P S295V 10.5A & H 42 C. 16 hr 35.4 106.6 S98P A136P Q169K S202R W260F L288I L294PS295V 10.5 A & H 42 C. 16 hr 31.2 95.7 S98P A136P E177S S202R W260FL288I L294P S295V 10.5 A & H 42 C. 16 hr 32.5 108.0 S98P A136P E177YS202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 38.1 102.1 S98PA136P N150T S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 34.1101.8 S98P A136P N150S S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16hr 34.7 108.7 S98P A136P N150R S202R W260F L288I L294P S295V 10.5 A & H42 C. 16 hr 42.0 128.3 S98P A136P Q184E S202R W260F L288I L294P S295V10.5 A & H 42 C. 16 hr 25.1 79.2 S98P A136P Q184K S202R W260F L288IL294P S295V 10.5 A & H 42 C. 16 hr 36.1 111.9 S98P A136P Q184S S202RW260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 26.3 86.1 S98P A136PR185G S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 29.4 94.3N18V H80K S98P A136P S202R W260F L288I L294P S295V 10.5 A & H 42 C. 40hr 21.1 175.2 H80K S95D S98P A136P S202R W260F L288I L294P S295V 10.5 A& H 42 C. 40 hr 37.4 273.2 H80K S98P A136P D139A S202R W260F L288I L294PS295V 10.5 A & H 42 C. 40 hr 23.9 197.5 H80K S98P A136P D139R S202RW260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 28.5 217.1 H80K S98PA136P S202R R210G W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 24.6196.4 S3P S98P A136P S202R G257A W260F L288I L294P S295V 10.5 A & H 42C. 40 hr 23.2 187.3 S8T S98P A136P S202R G257A W260F L288I L294P S295V10.5 A & H 42 C. 40 hr 26.0 202.8 N18V S98P A136P S202R G257A W260FL288I L294P S295V 10.5 A & H 42 C. 40 hr 26.6 210.5 T37R S98P A136PS202R G257A W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 22.4 181.6E41V S98P A136P S202R G257A W260F L288I L294P S295V 10.5 A & H 42 C. 40hr 20.3 172.2 R70K S98P A136P S202R G257A W260F L288I L294P S295V 10.5 A& H 42 C. 40 hr 22.2 187.0 D78G S98P A136P S202R G257A W260F L288I L294PS295V 10.5 A & H 42 C. 40 hr 29.6 214.7 A83S S98P A136P S202R G257AW260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 22.9 175.7 Y93F S98PA136P S202R G257A W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 28.3211.2 Y93Q S98P A136P S202R G257A W260F L288I L294P S295V 10.5 A & H 42C. 40 hr 34.9 247.4 S98P I114Q A136P S202R G257A W260F L288I L294P S295V10.5 A & H 42 C. 40 hr 21.8 182.5 S98P D118K A136P S202R G257A W260FL288I L294P S295V 10.5 A & H 42 C. 40 hr 25.6 197.7 S98P T119R A136PS202R G257A W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 22.3 167.0S98P A136P N150T S202R G257A W260F L288I L294P S295V 10.5 A & H 42 C. 40hr 21.8 182.5 S98P A136P N150S S202R G257A W260F L288I L294P S295V 10.5A & H 42 C. 40 hr 21.2 177.1 S98P A136P E177S S202R G257A W260F L288IL294P S295V 10.5 A & H 42 C. 40 hr 21.7 175.1 S98P A136P E177Y S202RG257A W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 20.4 167.9 S98PA136P Q184K S202R G257A W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr20.3 178.2 S95D S98P A136P S202R G257A W260F L288I L294P S295V 10.5 A &H 42 C. 40 hr 42.2 346.1 S95E S98P A136P S202R G257A W260F L288I L294PS295V 10.5 A & H 42 C. 40 hr 28.8 226.2 S98P A136P D139A S202R G257AW260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 33.5 249.4 S98P A136PN200T S202R G257A W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 26.9216.6 S98P A136P S202R R210L G257A W260F L288I L294P S295V 10.5 A & H 42C. 40 hr 20.9 167.8 S98P A136P S202R R210G G257A W260F L288I L294P S295V10.5 A & H 42 C. 40 hr 31.7 244.5 S98P A136P S202R E234Y G257A W260FL288I L294P S295V 10.5 A & H 42 C. 40 hr 33.4 255.0 S8T Y93Q D118K A136PS202R W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 31.4 240.1 N18VY93Q D118K A136P S202R W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr34.2 239.6 T37P Y93Q D118K A136P S202R W260F L288I L294P S295V 10.5 A &H 42 C. 40 hr 28.1 204.1 E41V Y93Q D118K A136P S202R W260F L288I L294PS295V 10.5 A & H 42 C. 40 hr 26.9 198.6 S74K Y93Q D118K A136P S202RW260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 20.8 179.9 D78G Y93QD118K A136P S202R W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 21.9180.8 H80K Y93Q D118K A136P S202R W260F L288I L294P S295V 10.5 A & H 42C. 40 hr 22.9 181.3 H80R Y93Q D118K A136P S202R W260F L288I L294P S295V10.5 A & H 42 C. 40 hr 22.2 170.8 A83S Y93Q D118K A136P S202R W260FL288I L294P S295V 10.5 A & H 42 C. 40 hr 22.6 178.5 Y93Q S98P D118KA136P S202R W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 29.3 216.7Y93Q S111A D118K A136P S202R W260F L288I L294P S295V 10.5 A & H 42 C. 40hr 21.4 181.7 Y93Q S111K D118K A136P S202R W260F L288I L294P S295V 10.5A & H 42 C. 40 hr 22.0 175.9 Y93Q D118K A136P N150T S202R W260F L288IL294P S295V 10.5 A & H 42 C. 40 hr 20.0 168.3 Y93Q D118K A136P N150SS202R W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 21.0 173.2 Y93QD118K A136P N150R S202R W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr21.9 183.7 Y93Q D118K A136P E177S S202R W260F L288I L294P S295V 10.5 A &H 42 C. 40 hr 20.8 174.5 Y93Q S95D D118K A136P S202R W260F L288I L294PS295V 10.5 A & H 42 C. 40 hr 53.6 424.5 Y93Q S95E D118K A136P S202RW260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 31.0 232.1 Y93Q D118KA136P D139A S202R W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 37.5259.4 Y93Q D118K A136P D139R S202R W260F L288I L294P S295V 10.5 A & H 42C. 40 hr 49.2 388.6 Y93Q D118K A136P D139V S202R W260F L288I L294P S295V10.5 A & H 42 C. 40 hr 26.7 191.0 Y93Q D118K A136P D139W S202R W260FL288I L294P S295V 10.5 A & H 42 C. 40 hr 27.2 208.7 Y93Q D118K A136PN200T S202R W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 26.0 188.9Y93Q D118K A136P S202R R210L W260F L288I L294P S295V 10.5 A & H 42 C. 40hr 23.8 182.2 Y93Q D118K A136P S202R R210M W260F L288I L294P S295V 10.5A & H 42 C. 40 hr 32.6 226.4 Y93Q D118K A136P S202R R210G W260F L288IL294P S295V 10.5 A & H 42 C. 40 hr 33.2 229.7 Y93Q D118K A136P S202RE234Y W260F L288I L294P S295V 10.5 A & H 42 C. 40 hr 35.5 256.8 T37PS98P A136P S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16 hr 33.598.9 H80R S98P A136P S202R W260F L288I L294P S295V 10.5 A & H 42 C. 16hr 36.1 103.3 V82I S98P A136P S202R W260F L288I L294P S295V 10.5 A & H42 C. 16 hr 39.2 118.0 V82I A83P A136P S202R W260F L288I L294P S295V10.5 A & H 42 C. 16 hr 24.0 77.5 Y93Q A136P D139A S202R W260F L288IL294P S295V S3P 10.5 A & H 44 C. 16 hr 22.1 182.3 Y93Q A136P D139A S202RW260F L288I L294P S295V N18V 10.5 A & H 44 C. 16 hr 24.1 193.8 Y93QA136P D139A S202R W260F L288I L294P S295V E41V 10.5 A & H 44 C. 16 hr25.2 193.7 Y93Q A136P D139A S202R W260F L288I L294P S295V V82I 10.5 A &H 44 C. 16 hr 21.3 174.0 Y93Q A136P D139A S202R W260F L288I L294P S295VS95D 10.5 A & H 44 C. 16 hr 48.6 378.5 Y93Q A136P D139A S202R W260FL288I L294P S295V S98P 10.5 A & H 44 C. 16 hr 22.4 176.3 Y93Q A136PD139A S202R W260F L288I L294P S295V R210M 10.5 A & H 44 C. 16 hr 25.9198.6 Y93Q A136P D139A S202R W260F L288I L294P S295V R210G 10.5 A & H 44C. 16 hr 35.4 255.2 Y93Q A136P D139A S202R W260F L288I L294P S295V E234Y10.5 A & H 44 C. 16 hr 27.3 209.1 Y93Q A136P D139A S202R W260F L288IL294P S295V N273D 10.5 A & H 44 C. 16 hr 20.0 174.6 Y93Q A136P D139AS202R W260F L288I L294P S295V N213V 10.5 A & H 44 C. 16 hr 21.8 182.4Y93Q A136P D139A S202R W260F L288I L294P S295V N213D 10.5 A & H 44 C. 16hr 21.2 165.1 H80K Y93Q A136P S202R W260F L288I L294P S295V S95D 10.5 A& H 44 C. 16 hr 32.9 251.1 H80K Y93Q A136P S202R W260F L288I L294P S295VD139R 10.5 A & H 44 C. 16 hr 25.2 192.5 H80K Y93Q A136P S202R W260FL288I L294P S295V E234Y 10.5 A & H 44 C. 16 hr 20.7 157.9 Y93Q A136PD139A S202R W260F L288I L294P S295V P183G 10.5 A & H 44 C. 16 hr 25.6191.3 Y93Q A136P D139A S202R W260F L288I L294P S295V P183T 10.5 A & H 44C. 16 hr 24.3 184.8 Y93Q A136P D139A S202R W260F L288I L294P S295V Q243E10.5 A & H 44 C. 16 hr 21.9 175.9 Y93Q A136P D139A S202R W260F L288IL294P S295V N283W 10.5 A & H 44 C. 16 hr 30.8 237.5 Y93Q A136P D139AS202R W260F L288I L294P S295V N283H 10.5 A & H 44 C. 16 hr 26.2 188.6Y93Q A136P D139A S202R W260F L288I L294P S295V A276W 10.5 A & H 44 C. 16hr 20.5 164.3 Y93Q A136P D139A S202R W260F L288I L294P S295V A276D 10.5A & H 44 C. 16 hr 26.6 193.6 Y93Q S95D D118K A136P S202R W260F N279DL288I L294P 10.5 A & H 44 C. 40 hr 38.2 676.4 S295V Y93Q S95D D118KA136P S202R W260F N279E L288I L294P 10.5 A & H 44 C. 40 hr 43.3 778.8S295V Y93Q S95D N100Y D118K A136P S202R W260F L288I L294P 10.5 A & H 44C. 40 hr 23.0 442.9 S295V Y93Q S95D D118K A136P S202R W260F N273E L288IL294P 10.5 A & H 44 C. 40 hr 30.7 551.0 S295V Y6H Y93Q S95D D118K A136PS202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 24.2 458.1 Y6M Y93QS95D D118K A136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr25.7 479.1 Y93Q S95D D118K A136P S202R N213V W260F L288I L294P 10.5 A &H 44 C. 40 hr 33.4 593.1 S295V Y93Q S95D D118K A136P S202R N213D W260FL288I L294P 10.5 A & H 44 C. 40 hr 34.2 608.0 S295V Y93Q S95D D118KA136P P183T S202R W260F L288I L294P 10.5 A & H 44 C. 40 hr 33.2 591.7S295V Y93Q S95D D118K A136P S202R W260F N272M L288I L294P 10.5 A & H 44C. 40 hr 25.1 452.9 S295V Y93Q S95D D118K A136P S202R W260F N272T L288IL294P 10.5 A & H 44 C. 40 hr 36.1 639.9 S295V Y93Q S95D D118K A136PS202R Q243K W260F L288I L294P 10.5 A & H 44 C. 40 hr 33.1 587.7 S295VY93Q S95D D118K A136P S202R Q243E W260F L288I L294P 10.5 A & H 44 C. 40hr 33.8 599.7 S295V Y93Q S95D D118K A136P S202R W260F N283W L288I L294P10.5 A & H 44 C. 40 hr 39.6 702.9 S295V Y93Q S95D D118K A136P S202RW260F N283H L288I L294P 10.5 A & H 44 C. 40 hr 42.6 764.9 S295V Y93QS95D D118K A136P S202R W260F A276E L288I L294P 10.5 A & H 44 C. 40 hr38.4 681.8 S295V Y93Q S95D D118K A136P S202R W260F A276W L288I L294P10.5 A & H 44 C. 40 hr 30.5 547.3 S295V Y93Q S95D D118K A136P S202RW260F A276D L288I L294P 10.5 A & H 44 C. 40 hr 34.9 617.1 S295V Y93QS95D D118K A136P S202R W260F T280L L288I L294P 10.5 A & H 44 C. 40 hr31.3 560.5 S295V S8T Y93Q S95D D118K A136P S202R W260F L288I L294P S295V10.5 A & H 44 C. 40 hr 33.3 592.3 N18V Y93Q S95D D118K A136P S202R W260FL288I L294P S295V 10.5 A & H 44 C. 40 hr 37.3 659.4 N18R Y93Q S95D D118KA136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 23.4 447.7T37P Y93Q S95D D118K A136P S202R W260F L288I L294P S295V 10.5 A & H 44C. 40 hr 26.7 492.9 T37R Y93Q S95D D118K A136P S202R W260F L288I L294PS295V 10.5 A & H 44 C. 40 hr 32.5 576.4 N45G Y93Q S95D D118K A136P S202RW260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 23.2 444.8 G47A Y93Q S95DD118K A136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 21.7425.5 G47K Y93Q S95D D118K A136P S202R W260F L288I L294P S295V 10.5 A &H 44 C. 40 hr 26.7 500.1 G47S Y93Q S95D D118K A136P S202R W260F L288IL294P S295V 10.5 A & H 44 C. 40 hr 27.4 484.9 D65E Y93Q S95D D118K A136PS202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 21.2 404.5 R70KY93Q S95D D118K A136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40hr 30.9 559.7 N71S Y93Q S95D D118K A136P S202R W260F L288I L294P S295V10.5 A & H 44 C. 40 hr 24.2 456.4 S74K Y93Q S95D D118K A136P S202R W260FL288I L294P S295V 10.5 A & H 44 C. 40 hr 27.8 508.2 Y93Q S95D S111AD118K A136P S202R W260F L288I L294P 10.5 A & H 44 C. 40 hr 23.8 452.6S295V Y93Q S95D S111K D118K A136P S202R W260F L288I L294P 10.5 A & H 44C. 40 hr 24.6 472.5 S295V Y93Q S95D S111R D118K A136P S202R W260F L288IL294P 10.5 A & H 44 C. 40 hr 22.6 437.8 S295V Y93Q S95D I114M D118KA136P S202R W260F L288I L294P 10.5 A & H 44 C. 40 hr 28.8 496.3 S295VY93Q S95D I114W D118K A136P S202R W260F L288I L294P 10.5 A & H 44 C. 40hr 25.8 461.9 S295V Y93Q S95D K116R D118K A136P S202R W260F L288I L294P10.5 A & H 44 C. 40 hr 22.8 466.1 S295V Y93Q S95D D118K T119R A136PS202R W260F L288I L294P 10.5 A & H 44 C. 40 hr 25.5 476.3 S295V Y93QS95D D118K A136P K142M S202R W260F L288I L294P 10.5 A & H 44 C. 40 hr21.1 390.1 S295V Y93Q S95D D118K A136P K142V S202R W260F L288I L294P10.5 A & H 44 C. 40 hr 23.7 451.4 S295V Y93Q S95D D118K A136P Q143RS202R W260F L288I L294P 10.5 A & H 44 C. 40 hr 22.0 390.7 S295V Y93QS95D D118K A136P N150T S202R W260F L288I L294P 10.5 A & H 44 C. 40 hr25.9 481.7 S295V Y93Q S95D D118K A136P N150S S202R W260F L288I L294P10.5 A & H 44 C. 40 hr 26.2 485.1 S295V Y93Q S95D D118K A136P N150RS202R W260F L288I L294P 10.5 A & H 44 C. 40 hr 26.2 474.2 S295V Y93QS95D D118K A136P Q169A S202R W260F L288I L294P 10.5 A & H 44 C. 40 hr28.3 516.6 S295V Y93Q S95D D118K A136P Q169R S202R W260F L288I L294P10.5 A & H 44 C. 40 hr 21.3 420.7 S295V Y93Q S95D D118K A136P Q169KS202R W260F L288I L294P 10.5 A & H 44 C. 40 hr 28.0 508.1 S295V Y93QS95D D118K A136P Y174R S202R W260F L288I L294P 10.5 A & H 44 C. 40 hr26.1 465.7 S295V Y93Q S95D D118K A136P Y174L S202R W260F L288I L294P10.5 A & H 44 C. 40 hr 25.1 449.6 S295V Y93Q S95D D118K A136P E177YS202R W260F L288I L294P 10.5 A & H 44 C. 40 hr 28.6 492.2 S295V Y93QS95D D118K A136P N180R S202R W260F L288I L294P 10.5 A & H 44 C. 40 hr26.7 478.1 S295V Y93Q S95D D118K A136P Q184E S202R W260F L288I L294P10.5 A & H 44 C. 40 hr 28.0 512.0 S295V Y93Q S95D D118K A136P Q184KS202R W260F L288I L294P 10.5 A & H 44 C. 40 hr 28.7 520.9 S295V Y93QS95D D118K A136P Q184S S202R W260F L288I L294P 10.5 A & H 44 C. 40 hr23.0 443.8 S295V Y93Q S95D D118K A136P R185G S202R W260F L288I L294P10.5 A & H 44 C. 40 hr 28.1 509.8 S295V Y93Q S95D D118K A136P S202RR210L W260F L288I L294P 10.5 A & H 44 C. 40 hr 34.5 611.4 S295V Y93QS95D D118K A136P S202R R210M W260F L288I L294P 10.5 A & H 44 C. 40 hr38.6 683.3 S295V Y93Q S95D D118K A136P S202R E234F W260F L288I L294P10.5 A & H 44 C. 40 hr 20.9 406.6 S295V Y93Q S95D D118K A136P S202RE234Y W260F L288I L294P 10.5 A & H 44 C. 40 hr 36.2 641.7 S295V Y93QS95D D118K A136P S202R A235R W260F L288I L294P 10.5 A & H 44 C. 40 hr27.4 452.8 S295V Y93Q S95D D118K A136P S202R A235K W260F L288I L294P10.5 A & H 44 C. 40 hr 25.6 457.9 S295V Y93Q S95D D118K A136P S202RR244K W260F L288I L294P 10.5 A & H 44 C. 40 hr 27.4 519.1 S295V E77NY93Q S95D D118K A136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40hr 24.9 452.4 E77T Y93Q S95D D118K A136P S202R W260F L288I L294P S295V10.5 A & H 44 C. 40 hr 23.1 418.0 D78G Y93Q S95D D118K A136P S202R W260FL288I L294P S295V 10.5 A & H 44 C. 40 hr 34.5 574.4 V82I Y93Q S95D D118KA136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 28.4 518.0Y6H Y93Q D118K A136P D139R S202R W260F L288I L294P S295V 10.5 A & H 44C. 24 hr 31.4 353.0 Y6M Y93Q D118K A136P D139R S202R W260F L288I L294P10.5 A & H 44 C. 24 hr 36.1 407.9 S295V Y93Q D118K A136P D139R S202RN213V W260F L288I L294P 10.5 A & H 44 C. 24 hr 40.2 440.2 S295V Y93QD118K A136P D139R S202R W260F N272T L288I L294P 10.5 A & H 44 C. 24 hr47.5 609.1 S295V Y93Q D118K A136P D139R S202R W260F T280L L288I L294P10.5 A & H 44 C. 24 hr 46.3 564.3 S295V N18V Y93Q D118K A136P D139RS202R W260F L288I L294P 10.5 A & H 44 C. 24 hr 38.9 458.3 S295V N18RY93Q D118K A136P D139R S202R W260F L288I L294P 10.5 A & H 44 C. 24 hr25.4 310.5 S295V T37R Y93Q D118K A136P D139R S202R W260F L288I L294P10.5 A & H 44 C. 24 hr 34.6 408.0 S295V E41V Y93Q D118K A136P D139RS202R W260F L288I L294P 10.5 A & H 44 C. 24 hr 37.5 449.7 S295V N45GY93Q D118K A136P D139R S202R W260F L288I L294P 10.5 A & H 44 C. 24 hr31.6 345.5 S295V G47A Y93Q D118K A136P D139R S202R W260F L288I L294P10.5 A & H 44 C. 24 hr 27.3 324.2 S295V G47K Y93Q D118K A136P D139RS202R W260F L288I L294P 10.5 A & H 44 C. 24 hr 24.5 294.3 S295V G47SY93Q D118K A136P D139R S202R W260F L288I L294P 10.5 A & H 44 C. 24 hr29.1 338.4 S295V R70K Y93Q D118K A136P D139R S202R W260F L288I L294P10.5 A & H 44 C. 24 hr 30.3 355.8 S295V N71S Y93Q D118K A136P D139RS202R W260F L288I L294P 10.5 A & H 44 C. 24 hr 22.1 278.1 S295V S74KY93Q D118K A136P D139R S202R W260F L288I L294P 10.5 A & H 44 C. 24 hr36.5 424.5 S295V Y93Q S111A D118K A136P D139R S202R W260F L288I L294P10.5 A & H 44 C. 24 hr 27.5 330.0 S295V Y93Q S111K D118K A136P D139RS202R W260F L288I L294P 10.5 A & H 44 C. 24 hr 26.5 306.8 S295V Y93QS111R D118K A136P D139R S202R W260F L288I L294P 10.5 A & H 44 C. 24 hr24.8 303.1 S295V Y93Q I114Q D118K A136P D139R S202R W260F L288I L294P10.5 A & H 44 C. 24 hr 27.6 331.8 S295V Y93Q I114W D118K A136P D139RS202R W260F L288I L294P 10.5 A & H 44 C. 24 hr 28.1 316.5 S295V Y93QK116R D118K A136P D139R S202R W260F L288I L294P 10.5 A & H 44 C. 24 hr22.3 276.9 S295V Y93Q D118K T119R A136P D139R S202R W260F L288I L294P10.5 A & H 44 C. 24 hr 23.6 277.4 S295V Y93Q D118K A136P D139R K142MS202R W260F L288I L294P 10.5 A & H 44 C. 24 hr 32.1 367.8 S295V Y93QD118K A136P D139R N150R S202R W260F L288I L294P 10.5 A & H 44 C. 24 hr33.2 375.8 S295V Y93Q D118K A136P D139R Q169A S202R W260F L288I L294P10.5 A & H 44 C. 24 hr 24.2 289.5 S295V Y93Q D118K A136P D139R Q169RS202R W260F L288I L294P 10.5 A & H 44 C. 24 hr 31.3 341.2 S295V Y93QD118K A136P D139R Q169K S202R W260F L288I L294P 10.5 A & H 44 C. 24 hr27.1 316.2 S295V Y93Q D118K A136P D139R E177Y S202R W260F L288I L294P10.5 A & H 44 C. 24 hr 35.7 412.0 S295V Y93Q D118K A136P D139R Q184ES202R W260F L288I L294P 10.5 A & H 44 C. 24 hr 29.0 335.0 S295V Y93QD118K A136P D139R Q184K S202R W260F L288I L294P 10.5 A & H 44 C. 24 hr28.9 335.7 S295V Y93Q D118K A136P D139R Q184S S202R W260F L288I L294P10.5 A & H 44 C. 24 hr 26.1 316.2 S295V Y93Q D118K A136P D139R S202RR210G W260F L288I L294P 10.5 A & H 44 C. 24 hr 57.2 742.1 S295V Y93QD118K A136P D139R S202R E234Y W260F L288I L294P 10.5 A & H 44 C. 24 hr53.3 666.5 S295V Y93Q D118K A136P D139R S202R A235K W260F L288I L294P10.5 A & H 44 C. 24 hr 28.9 340.3 S295V E77T Y93Q D118K A136P D139RS202R W260F L288I L294P 10.5 A & H 44 C. 24 hr 20.5 282.8 S295V D78GY93Q D118K A136P D139R S202R W260F L288I L294P 10.5 A & H 44 C. 24 hr32.2 368.4 S295V V82I Y93Q D118K A136P D139R S202R W260F L288I L294P10.5 A & H 44 C. 24 hr 33.5 372.5 S295V S95D S98P A136P S202R N213VG257A W260F L288I L294P 10.5 A & H 44 C. 24 hr 32.0 360.2 S295V S95DS98P A136P S202R G257A W260F N272M L288I L294P 10.5 A & H 44 C. 24 hr23.8 267.3 S295V S95D S98P A136P S202R G257A W260F N272T L288I L294P10.5 A & H 44 C. 24 hr 34.3 383.6 S295V S95D S98P A136P S202R Q243KG257A W260F L288I L294P 10.5 A & H 44 C. 24 hr 36.1 408.4 S295V S95DS98P A136P S202R G257A W260F N283W L288I L294P 10.5 A & H 44 C. 24 hr36.0 401.9 S295V S95D S98P A136P S202R G257A W260F A276E L288I L294P10.5 A & H 44 C. 24 hr 37.1 399.6 S295V S95D S98P A136P S202R G257AW260F A276W L288I L294P 10.5 A & H 44 C. 24 hr 30.4 344.8 S295V S95DS98P A136P S202R G257A W260F A276D L288I L294P 10.5 A & H 44 C. 24 hr33.1 385.6 S295V S8T S95D S98P A136P S202R G257A W260F L288I L294P S295V10.5 A & H 44 C. 24 hr 25.6 305.4 N18V S95D S98P A136P S202R G257A W260FL288I L294P S295V 10.5 A & H 44 C. 24 hr 31.2 366.4 N18R S95D S98P A136PS202R G257A W260F L288I L294P S295V 10.5 A & H 44 C. 24 hr 21.4 257.3T37R S95D S98P A136P S202R G257A W260F L288I L294P S295V 10.5 A & H 44C. 24 hr 31.3 341.3 E41V S95D S98P A136P S202R G257A W260F L288I L294PS295V 10.5 A & H 44 C. 24 hr 32.2 360.2 N45G S95D S98P A136P S202R G257AW260F L288I L294P S295V 10.5 A & H 44 C. 24 hr 24.6 289.4 G47A S95D S98PA136P S202R G257A W260F L288I L294P S295V 10.5 A & H 44 C. 24 hr 21.6268.8 G47K S95D S98P A136P S202R G257A W260F L288I L294P S295V 10.5 A &H 44 C. 24 hr 24.9 304.0 G47S S95D S98P A136P S202R G257A W260F L288IL294P S295V 10.5 A & H 44 C. 24 hr 25.2 285.1 R70K S95D S98P A136P S202RG257A W260F L288I L294P S295V 10.5 A & H 44 C. 24 hr 28.5 330.1 S74KS95D S98P A136P S202R G257A W260F L288I L294P S295V 10.5 A & H 44 C. 24hr 25.2 302.9 S95D S98P S111A A136P S202R G257A W260F L288I L294P 10.5 A& H 44 C. 24 hr 21.1 274.4 S295V S95D S98P S111R A136P S202R G257A W260FL288I L294P 10.5 A & H 44 C. 24 hr 24.6 297.3 S295V S95D S98P I114MA136P S202R G257A W260F L288I L294P 10.5 A & H 44 C. 24 hr 20.4 269.4S295V S95D S98P K116R A136P S202R G257A W260F L288I L294P 10.5 A & H 44C. 24 hr 22.3 274.5 S295V S95D S98P D118K A136P S202R G257A W260F L288IL294P 10.5 A & H 44 C. 24 hr 26.6 332.0 S295V S95D S98P T119R A136PS202R G257A W260F L288I L294P 10.5 A & H 44 C. 24 hr 24.7 300.0 S295VS95D S98P A136P K142M S202R G257A W260F L288I L294P 10.5 A & H 44 C. 24hr 20.7 267.0 S295V S95D S98P A136P N150S S202R G257A W260F L288I L294P10.5 A & H 44 C. 24 hr 24.8 300.9 S295V S95D S98P A136P N150R S202RG257A W260F L288I L294P 10.5 A & H 44 C. 24 hr 24.6 294.2 S295V S95DS98P A136P Q169A S202R G257A W260F L288I L294P 10.5 A & H 44 C. 24 hr20.2 266.7 S295V S95D S98P A136P Y174R S202R G257A W260F L288I L294P10.5 A & H 44 C. 24 hr 24.3 283.3 S295V S95D S98P A136P Y174L S202RG257A W260F L288I L294P 10.5 A & H 44 C. 24 hr 21.2 268.9 S295V S95DS98P A136P E177Y S202R G257A W260F L288I L294P 10.5 A & H 44 C. 24 hr25.0 313.8 S295V S95D S98P A136P N180R S202R G257A W260F L288I L294P10.5 A & H 44 C. 24 hr 22.4 268.3 S295V S95D S98P A136P Q184K S202RG257A W260F L288I L294P 10.5 A & H 44 C. 24 hr 22.4 273.5 S295V S95DS98P A136P S202R E234F G257A W260F L288I L294P 10.5 A & H 44 C. 24 hr24.5 300.8 S295V S95D S98P A136P S202R E234Y G257A W260F L288I L294P10.5 A & H 44 C. 24 hr 43.5 501.3 S295V E77T S95D S98P A136P S202R G257AW260F L288I L294P S295V 10.5 A & H 44 C. 24 hr 28.0 315.7 D78G S95D S98PA136P S202R G257A W260F L288I L294P S295V 10.5 A & H 44 C. 24 hr 25.0311.5 V82I S95D S98P A136P S202R G257A W260F L288I L294P S295V 10.5 A &H 44 C. 24 hr 29.8 338.1 H80K S95D S98P A136P S202R W260F N279E L288IL294P S295V 10.5 A & H 44 C. 16 hr 28.6 204.7 H80K S95D S98P A136P S202RW260F N273D L288I L294P S295V 10.5 A & H 44 C. 16 hr 22.5 165.5 H80KS95D S98P A136P S202R W260F N273E L288I L294P S295V 10.5 A & H 44 C. 16hr 20.8 164.5 H80K S95D S98P A136P S202R N213V W260F L288I L294P S295V10.5 A & H 44 C. 16 hr 23.5 183.7 H80K S95D S98P A136P P183T S202R W260FL288I L294P S295V 10.5 A & H 44 C. 16 hr 29.4 216.7 H80K S95D S98P A136PS202R Q243K W260F L288I L294P S295V 10.5 A & H 44 C. 16 hr 25.1 185.6H80K S95D S98P A136P S202R W260F N283W L288I L294P 10.5 A & H 44 C. 16hr 30.1 221.8 S295V H80K S95D S98P A136P S202R W260F N283H L288I L294PS295V 10.5 A & H 44 C. 16 hr 29.2 208.4 H80K S95D S98P A136P S202R W260FA276E L288I L294P S295V 10.5 A & H 44 C. 16 hr 25.4 188.3 H80K S95D S98PA136P S202R W260F A276D L288I L294P S295V 10.5 A & H 44 C. 16 hr 24.8191.2 H80K S95D S98P A136P S202R W260F T280L L288I L294P S295V 10.5 A &H 44 C. 16 hr 20.0 158.9 N18V H80K S95D S98P A136P S202R W260F L288IL294P S295V 10.5 A & H 44 C. 16 hr 24.0 185.2 T37P H80K S95D S98P A136PS202R W260F L288I L294P S295V 10.5 A & H 44 C. 16 hr 21.7 169.8 T37RH80K S95D S98P A136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 16hr 21.1 178.8 E41V H80K S95D S98P A136P S202R W260F L288I L294P S295V10.5 A & H 44 C. 16 hr 23.0 174.4 H80K S95D S98P D118K A136P S202R W260FL288I L294P S295V 10.5 A & H 44 C. 16 hr 21.8 180.1 H80K S95D S98P A136PN150R S202R W260F L288I L294P S295V 10.5 A & H 44 C. 16 hr 20.1 155.3H80K S95D S98P A136P S202R R210L W260F L288I L294P S295V 10.5 A & H 44C. 16 hr 26.5 197.2 H80K S95D S98P A136P S202R R210M W260F L288I L294PS295V 10.5 A & H 44 C. 16 hr 33.4 242.3 H80K S95D S98P A136P S202R R210GW260F L288I L294P S295V 10.5 A & H 44 C. 16 hr 32.7 221.3 H80K S95D S98PA136P S202R E234Y W260F L288I L294P S295V 10.5 A & H 44 C. 16 hr 34.7233.6 H80K S95D S98P A136P D139A S202R W260F L288I L294P S295V 10.5 A &H 44 C. 16 hr 37.0 254.3 S95D S98P A136P D139A S202R G257A W260F L288IL294P 10.5 A & H 44 C. 16 hr 42.6 268.1 S295V A1G H80K Y93Q S95D A136PS202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 25.1 486.8 H80KY93Q S95D A136P S202R Q243K W260F L288I L294P S295V 10.5 A & H 44 C. 40hr 30.6 573.7 S3P H80K Y93Q S95D A136P S202R W260F L288I L294P S295V10.5 A & H 44 C. 40 hr 21.3 447.3 T37P H80K Y93Q S95D A136P S202R W260FL288I L294P S295V 10.5 A & H 44 C. 40 hr 22.4 474.6 G47A H80K Y93Q S95DA136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 35.9 694.5S8T H80K Y93Q S95D A136P S202R W260F L288I L294P S295V 10.5 A & H 44 C.40 hr 26.6 510.9 H80K Y93Q S95D A136P S202R W260F A276E L288I L294PS295V 10.5 A & H 44 C. 40 hr 29.1 540.3 H80K Y93Q S95D T119R A136P S202RW260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 23.4 467.2 H80K Y93Q S95DD118K A136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 36.8661.6 E41V H80K Y93Q S95D A136P S202R W260F L288I L294P S295V 10.5 A & H44 C. 40 hr 27.6 523.6 T37R H80K Y93Q S95D A136P S202R W260F L288I L294PS295V 10.5 A & H 44 C. 40 hr 21.1 441.1 R70K H80K Y93Q S95D A136P S202RW260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 20.4 447.2 N18V H80K Y93QS95D A136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 26.0492.0 S74K H80K Y93Q S95D A136P S202R W260F L288I L294P S295V 10.5 A & H44 C. 40 hr 22.5 440.5 H80K Y93Q S95D A136P N150T S202R W260F L288IL294P S295V 10.5 A & H 44 C. 40 hr 20.5 437.8 H80K Y93Q S95D A136P N150RS202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 24.4 458.1 H80KY93Q S95D A136P Q184E S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40hr 20.2 430.9 H80K Y93Q S95D A136P S202R R210L W260F L288I L294P S295V10.5 A & H 44 C. 40 hr 27.1 522.3 H80K Y93Q S95D A136P S202R R210M W260FL288I L294P 10.5 A & H 44 C. 40 hr 31.1 590.9 S295V H80K Y93Q S95D A136PS202R R210G W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 33.9 627.4H80K Y93Q S95D A136P D139W S202R W260F L288I L294P 10.5 A & H 44 C. 40hr 21.6 432.4 S295V H80K Y93Q S95D A136P N200T S202R W260F L288I L294PS295V 10.5 A & H 44 C. 40 hr 27.7 499.4 D78G H80K Y93Q S95D A136P S202RW260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 22.2 463.6 H80K V82I Y93QS95D A136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 24.8488.1 H80K Y93Q S95D A136P S202R W260F N279D L288I L294P S295V 10.5 A &H 44 C. 40 hr 27.7 535.0 H80K Y93Q S95D A136P S202R W260F N279E L288IL294P S295V 10.5 A & H 44 C. 40 hr 37.6 678.9 H80K Y93Q S95D A136P S202RW260F N273D L288I L294P S295V 10.5 A & H 44 C. 40 hr 24.8 494.0 Y6H H80KY93Q S95D A136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr20.6 431.0 Y6M H80K Y93Q S95D A136P S202R W260F L288I L294P S295V 10.5 A& H 44 C. 40 hr 21.3 428.5 H80K Y93Q S95D A136P S202R N213V W260F L288IL294P S295V 10.5 A & H 44 C. 40 hr 24.6 486.5 H80K Y93Q S95D A136P S202RN213D W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 28.6 551.5 H80KY93Q S95D A136P P183G S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40hr 29.8 575.6 H80K Y93Q S95D A136P P183T S202R W260F L288I L294P S295V10.5 A & H 44 C. 40 hr 31.1 610.2 H80K Y93Q S95D A136P S202R W260F L288IL294P S295V 10.5 A & H 44 C. 40 hr 23.1 467.4 S95D A136P S202R Q243EW260F L288I L294P S295V 10.5 A & H 44 C. 16 hr 22.1 181.9 S95D A136PS202R Q243K W260F L288I L294P S295V 10.5 A & H 44 C. 16 hr 28.1 204.7T37P S95D A136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 16 hr21.8 173.3 G47S S95D A136P S202R W260F L288I L294P S295V 10.5 A & H 44C. 16 hr 20.1 166.9 H80K S95D A136P S202R W260F L288I L294P S295V 10.5 A& H 44 C. 16 hr 20.9 175.8 G47K S95D A136P S202R W260F L288I L294P S295V10.5 A & H 44 C. 16 hr 20.0 162.7 S95D T119R A136P S202R W260F L288IL294P S295V 10.5 A & H 44 C. 16 hr 21.5 174.9 H80R S95D A136P S202RW260F L288I L294P S295V 10.5 A & H 44 C. 16 hr 20.2 163.9 S95D D118KA136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 16 hr 21.8 173.5D78G S95D A136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 16 hr22.6 174.5 S95D I114Q A136P S202R W260F L288I L294P S295V 10.5 A & H 44C. 16 hr 24.7 175.2 S95D I114W A136P S202R W260F L288I L294P S295V 10.5A & H 44 C. 16 hr 27.8 203.6 T37R S95D A136P S202R W260F L288I L294PS295V 10.5 A & H 44 C. 16 hr 23.2 184.6 R70K S95D A136P S202R W260FL288I L294P S295V 10.5 A & H 44 C. 16 hr 25.6 186.9 N18V S95D A136PS202R W260F L288I L294P S295V 10.5 A & H 44 C. 16 hr 33.8 210.9 S74KS95D A136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 16 hr 20.8167.1 S95D A136P Q169A S202R W260F L288I L294P S295V 10.5 A & H 44 C. 16hr 21.9 163.1 S95D A136P Q169K S202R W260F L288I L294P S295V 10.5 A & H44 C. 16 hr 21.2 147.5 S95D A136P E177Y S202R W260F L288I L294P S295V10.5 A & H 44 C. 16 hr 21.2 171.3 S95D A136P N150T S202R W260F L288IL294P S295V 10.5 A & H 44 C. 16 hr 24.2 209.2 S95D A136P N150S S202RW260F L288I L294P S295V 10.5 A & H 44 C. 16 hr 22.0 168.1 S95D A136PN150R S202R W260F L288I L294P S295V 10.5 A & H 44 C. 16 hr 23.9 187.2S95D A136P Q184E S202R W260F L288I L294P S295V 10.5 A & H 44 C. 16 hr23.9 204.2 S95D A136P S202R R210L W260F L288I L294P S295V 10.5 A & H 44C. 16 hr 23.7 188.1 S95D A136P S202R R210M W260F L288I L294P S295V 10.5A & H 44 C. 16 hr 33.0 246.3 S95D A136P D139V S202R W260F L288I L294PS295V 10.5 A & H 44 C. 16 hr 24.0 196.0 S95D A136P N200T S202R W260FL288I L294P S295V 10.5 A & H 44 C. 16 hr 29.1 207.9 S95D A136P S202RW260F N273D L288I L294P S295V 10.5 A & H 44 C. 16 hr 25.4 200.8 Y6M S95DA136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 16 hr 21.9 181.7S95D A136P P183G S202R W260F L288I L294P S295V 10.5 A & H 44 C. 16 hr33.3 243.1 S95D A136P P183T S202R W260F L288I L294P S295V 10.5 A & H 44C. 16 hr 30.5 236.4 S95D A136P S202R W260F T280L L288I L294P S295V 10.5A & H 44 C. 16 hr 33.0 200.0 H80K Y93Q S95D A136P S202R W260F N272ML288I L294P 10.5 A & H 44 C. 16 hr 41.1 286.1 S295V H80K Y93Q S95D A136PS202R W260F N272T L288I L294P S295V 10.5 A & H 44 C. 16 hr 52.7 352.7H80K Y93Q S95D A136P S202R W260F N283W L288I L294P 10.5 A & H 44 C. 16hr 59.1 451.0 S295V H80K Y93Q S95D A136P S202R W260F N283H L288I L294PS295V 10.5 A & H 44 C. 16 hr 57.9 416.0 H80K Y93Q S95D A136P S202R W260FA276D L288I L294P S295V 10.5 A & H 44 C. 16 hr 58.0 413.6 S95D E133RA136P S202R W260F L288I L294P S295V 10.5 A & H 44 C. 16 hr 21.7 178.3H80K Y93Q S95D A136P S202R W260F T280L L288I L294P S295V 10.5 A & H 44C. 16 hr 53.0 453.0 H80K Y93Q D118K A136P D139R S202R W260F L288I L294P10.5 A & H 44 C. 16 hr 39.1 279.1 S295V Y93Q S95D D118K A136P D139RS202R W260F L288I L294P 10.5 A & H 44 C. 16 hr 44.9 351.9 S295V A1G Y93QS95D A136P D139A S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr28.8 574.9 Y93Q S95D A136P D139A S202R Q243E W260F L288I L294P 10.5 A &H 44 C. 40 hr 28.9 548.1 S295V Y93Q S95D A136P D139A S202R Q243K W260FL288I L294P 10.5 A & H 44 C. 40 hr 32.0 570.1 S295V Y93Q S95D K116RA136P D139A S202R W260F L288I L294P 10.5 A & H 44 C. 40 hr 21.7 423.3S295V S3P Y93Q S95D A136P D139A S202R W260F L288I L294P S295V 10.5 A & H44 C. 40 hr 24.0 444.5 T37P Y93Q S95D A136P D139A S202R W260F L288IL294P S295V 10.5 A & H 44 C. 40 hr 20.9 450.2 H80K Y93Q S95D A136P D139AS202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 21.3 435.4 Y93QS95D A136P D139A S202R W260F A276E L288I L294P 10.5 A & H 44 C. 40 hr30.2 571.6 S295V Y93Q S95D A136P D139A S202R G257A W260F L288I L294P10.5 A & H 44 C. 40 hr 34.0 615.0 S295V Y93Q S95D T119R A136P D139AS202R W260F L288I L294P 10.5 A & H 44 C. 40 hr 20.4 449.5 S295V D78GY93Q S95D A136P D139A S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40hr 25.5 497.1 E41V Y93Q S95D A136P D139A S202R W260F L288I L294P S295V10.5 A & H 44 C. 40 hr 35.4 643.8 Y93Q S95D S111A A136P D139A S202RW260F L288I L294P 10.5 A & H 44 C. 40 hr 20.7 442.1 S295V Y93Q S95DA136P D139R S202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 25.6476.8 R70K Y93Q S95D A136P D139A S202R W260F L288I L294P S295V 10.5 A &H 44 C. 40 hr 21.1 428.8 N18V Y93Q S95D A136P D139A S202R W260F L288IL294P S295V 10.5 A & H 44 C. 40 hr 27.8 559.0 S74K Y93Q S95D A136P D139AS202R W260F L288I L294P S295V 10.5 A & H 44 C. 40 hr 22.8 454.1 Y93QS95D A136P D139A E177Y S202R W260F L288I L294P 10.5 A & H 44 C. 40 hr24.4 479.1 S295V Y93Q S95D A136P D139A N150S S202R W260F L288I L294P10.5 A & H 44 C. 40 hr 22.6 491.3 S295V Y93Q S95D A136P D139A N150RS202R W260F L288I L294P 10.5 A & H 44 C. 40 hr 21.2 458.7 S295V Y93QS95D A136P D139A R185G S202R W260F L288I L294P 10.5 A & H 44 C. 40 hr22.0 445.1 S295V Y93Q S95D A136P D139A S202R R210M W260F L288I L294P10.5 A & H 44 C. 40 hr 26.8 504.2 S295V Y93Q S95D A136P D139A S202RR210G W260F L288I L294P 10.5 A & H 44 C. 40 hr 28.7 536.7 S295V Y93QS95D A136P D139A N200T S202R W260F L288I L294P 10.5 A & H 44 C. 40 hr20.2 424.6 S295V Y93Q S95D A136P D139A S202R W260F N279E L288I L294P10.5 A & H 44 C. 40 hr 34.0 565.9 S295V Y93Q S95D A136P D139A S202RN213V W260F L288I L294P 10.5 A & H 44 C. 40 hr 24.2 467.1 S295V Y93QS95D A136P D139A S202R N213D W260F L288I L294P 10.5 A & H 44 C. 40 hr24.0 440.2 S295V Y93Q S95D A136P D139A P183G S202R W260F L288I L294P10.5 A & H 44 C. 40 hr 25.3 474.1 S295V Y93Q S95D A136P D139A P183TS202R W260F L288I L294P 10.5 A & H 44 C. 40 hr 27.6 481.6 S295V Y93QS95D A136P D139A S202R W260F N272M L288I L294P 10.5 A & H 44 C. 40 hr23.0 488.3 S295V Y93Q S95D A136P D139A S202R W260F N272T L288I L294P10.5 A & H 44 C. 40 hr 27.2 500.7 S295V Y93Q S95D A136P D139A S202RW260F N283W L288I L294P 10.5 A & H 44 C. 40 hr 30.0 570.6 S295V Y93QS95D A136P D139A S202R W260F N283H L288I L294P 10.5 A & H 44 C. 40 hr30.2 531.6 S295V Y93Q S95D A136P D139A S202R W260F A276W L288I L294P10.5 A & H 44 C. 40 hr 24.1 477.8 S295V Y93Q S95D A136P D139A S202RW260F A276D L288I L294P 10.5 A & H 44 C. 40 hr 25.7 517.0 S295V Y93QS95D A136P D139A S202R W260F T280L L288I L294P 10.5 A & H 44 C. 40 hr27.3 488.8 S295V Y93Q S95D A136P D139A S202R W260F L288I L294P S295V10.5 A & H 44 C. 40 hr 27.6 531.3 A1V Y93Q D118K A136P D139R S202R R210GG257A W260F 10.5 A & H 44 C. 40 hr 52.2 1118.4 A276D L288I L294P S295VY93Q D118K A136P D139R S202R R210G Q243K W260F L288I 10.5 A & H 44 C. 40hr 31.8 621.3 L294P S295V S3P Y93Q D118K A136P D139R S202R R210G W260FL288I 10.5 A & H 44 C. 40 hr 30.8 593.5 L294P S295V T37P Y93Q D118KA136P D139R S202R R210G W260F L288I 10.5 A & H 44 C. 40 hr 24.9 492.9L294P S295V S8T Y93Q D118K A136P D139R S202R R210G W260F L288I L294P10.5 A & H 44 C. 40 hr 27.7 530.8 S295V G47S Y93Q D118K A136P D139RS202R R210G W260F L288I 10.5 A & H 44 C. 40 hr 28.0 528.3 L294P S295VH80K Y93Q D118K A136P D139R S202R R210G W260F L288I 10.5 A & H 44 C. 40hr 25.2 496.3 L294P S295V Y93Q D118K A136P D139R S202R R210G W260F A276EL288I 10.5 A & H 44 C. 40 hr 32.1 629.1 L294P S295V E77N Y93Q D118KA136P D139R S202R R210G W260F L288I 10.5 A & H 44 C. 40 hr 23.8 482.1L294P S295V G47K S95D S98P D118K A136P D139R S202R R210G W260F 10.5 A &H 44 C. 40 hr 42.2 806.1 L288I L294P S295V E41V Y93Q D118K A136P D139RS202R R210G W260F L288I 10.5 A & H 44 C. 40 hr 29.1 541.9 L294P S295VT37R Y93Q D118K A136P D139R S202R R210G W260F L288I 10.5 A & H 44 C. 40hr 23.8 471.7 L294P S295V R70K Y93Q D118K A136P D139R S202R R210G W260FL288I 10.5 A & H 44 C. 40 hr 31.8 617.8 L294P S295V N45G Y93Q D118KA136P D139R S202R R210G W260F L288I 10.5 A & H 44 C. 40 hr 37.9 719.5L294P S295V N18V Y93Q D118K A136P D139R S202R R210G W260F L288I 10.5 A &H 44 C. 40 hr 36.8 678.6 L294P S295V Y93Q D118K A136P D139R N180R S202RR210G W260F L288I 10.5 A & H 44 C. 40 hr 27.6 511.2 L294P S295V Y93QD118K A136P D139R E177S S202R R210G W260F L288I 10.5 A & H 44 C. 40 hr25.3 483.6 L294P S295V Y93Q D118K A136P D139R E177Y S202R R210G W260FL288I 10.5 A & H 44 C. 40 hr 35.6 689.9 L294P S295V Y93Q D118K A136PD139R N150T S202R R210G W260F L288I 10.5 A & H 44 C. 40 hr 25.8 491.2L294P S295V Y93Q D118K A136P D139R N150S S202R R210G W260F L288I 10.5 A& H 44 C. 40 hr 24.9 513.3 L294P S295V Y93Q D118K A136P D139R S202RR210G E234F G257A W260F 10.5 A & H 44 C. 40 hr 42.1 810.5 A276D L288IL294P S295V Y93Q D118K A136P D139R S202R R210G E234Y W260F L288I 10.5 A& H 44 C. 40 hr 42.0 768.5 L294P S295V Y93Q D118K A136P D139R S202RR210G A235K W260F L288I 10.5 A & H 44 C. 40 hr 35.6 625.3 L294P S295VY93Q D118K A136P D139R S202R R210G R244K G257A W260F 10.5 A & H 44 C. 40hr 50.2 973.3 A276D L288I L294P S295V Y93Q S95D D118K A136P D139R S202RR210G W260F L288I 10.5 A & H 44 C. 40 hr 58.7 1181.5 L294P S295V Y93QA97S D118K A136P D139R S202R R210G G257A W260F 10.5 A & H 44 C. 40 hr43.7 865.9 A276D L288I L294P S295V Y93Q D118K A136P D139R N200T S202RR210G W260F L288I 10.5 A & H 44 C. 40 hr 23.1 477.4 L294P S295V G47AY93Q S95D D118K A136P S202R W260F N279E L288I L294P 10.5 A & H 46 C. 18hr 27.3 415.2 S295V G47S Y93Q S95D D118K A136P S202R W260F N279E L288IL294P 10.5 A & H 46 C. 18 hr 28.2 427.4 S295V V82I Y93Q S95D D118K A136PS202R W260F N279E L288I L294P 10.5 A & H 46 C. 18 hr 36.9 559.0 S295VE77N Y93Q S95D D118K A136P S202R W260F N279E L288I L294P 10.5 A & H 46C. 18 hr 24.9 392.9 S295V H80R Y93Q S95D D118K A136P S202R W260F N279EL288I L294P 10.5 A & H 46 C. 18 hr 38.7 564.9 S295V D78G Y93Q S95D D118KA136P S202R W260F N279E L288I 10.5 A & H 46 C. 18 hr 39.6 575.2 L294PS295V E41V Y93Q S95D D118K A136P S202R W260F N279E L288I L294P 10.5 A &H 46 C. 18 hr 38.2 605.8 S295V Y93Q S95D D104G D118K A136P S202R W260FN279E L288I 10.5 A & H 46 C. 18 hr 22.5 351.1 L294P S295V Y93Q S95DS111A D118K A136P S202R W260F N279E L288I 10.5 A & H 46 C. 18 hr 32.2489.6 L294P S295V Y93Q S95D S111R D118K A136P S202R W260F N279E L288I10.5 A & H 46 C. 18 hr 26.7 411.3 L294P S295V Y93Q S95D S111K D118KA136P S202R W260F N279E L288I 10.5 A & H 46 C. 18 hr 27.9 435.8 L294PS295V D65E Y93Q S95D D118K A136P S202R W260F N279E L288I L294P 10.5 A &H 46 C. 18 hr 33.9 512.7 S295V R70K Y93Q S95D D118K A136P S202R W260FN279E L288I L294P 10.5 A & H 46 C. 18 hr 34.2 550.2 S295V N18V Y93Q S95DD118K A136P S202R W260F N279E L288I L294P 10.5 A & H 46 C. 18 hr 37.6537.4 S295V S74K Y93Q S95D D118K A136P S202R W260F N279E L288I L294P10.5 A & H 46 C. 18 hr 33.0 486.7 S295V Y93Q S95D D118K A136P Y174RS202R W260F N279E L288I 10.5 A & H 46 C. 18 hr 28.8 418.6 L294P S295VY93Q S95D D118K A136P Q169A S202R W260F N279E L288I 10.5 A & H 46 C. 18hr 33.7 500.9 L294P S295V Y93Q S95D D118K A136P E177S S202R W260F N279EL288I 10.5 A & H 46 C. 18 hr 30.0 466.4 L294P S295V Y93Q S95D D118KA136P E177Y S202R W260F N279E L288I 10.5 A & H 46 C. 18 hr 32.0 505.7L294P S295V Y93Q S95D D118K T119R A136P S202R W260F N279E L288I 10.5 A &H 46 C. 18 hr 22.1 348.7 L294P S295V Y93Q S95D D118K A136P P183T S202RW260F N279E L288I 10.5 A & H 46 C. 18 hr 39.4 564.8 L294P S295V V82IY93Q S95D D118K A136P S202R W260F N283H L288I L294P 10.5 A & H 46 C. 18hr 36.8 588.0 S295V Y93Q S95D A136P D139A S202R E234Y Q243E W260F A276E10.5 A & H 46 C. 18 hr 64.3 1328.1 N279E L288I L294P S295V Y93Q S95DD118K A136P D139A S202R E234Y A235K Q243E 10.5 A & H 46 C. 18 hr 70.71454.5 W260F A276E N279E N283W L288I L294P S295V Y93Q S95D A136P D139AS202R E234Y A235K Q243E W260F 10.5 A & H 46 C. 18 hr 65.9 1454.5 A276EN279E L288I L294P S295V A1G Y93Q S95D D118K A136P S202R W260F N279EL288I L294P 10.5 A & H 46 C. 16 hr 25.9 687.7 S295V A1V Y93Q S95D D118KA136P S202R W260F N279E L288I L294P 10.5 A & H 46 C. 16 hr 22.6 663.8S295V Y93Q S95D D118K A136P S202R Q243Y W260F N279E L288I 10.5 A & H 46C. 16 hr 32.4 851.1 L294P S295V Y93Q S95D D118K A136P S202R Q243E W260FN279E L288I 10.5 A & H 46 C. 16 hr 27.8 720.9 L294P S295V Y93Q S95DD118K A136P S202R Q243K W260F N279E L288I 10.5 A & H 46 C. 16 hr 31.3823.0 L294P S295V Y93Q S95D D118K A136P S202R Q243H W260F N279E L288I10.5 A & H 46 C. 16 hr 20.1 537.2 L294P S295V S3P Y93Q S95D D118K A136PS202R W260F N279E L288I L294P 10.5 A & H 46 C. 16 hr 27.8 719.7 S295VT37P Y93Q S95D D118K A136P S202R W260F N279E L288I L294P 10.5 A & H 46C. 16 hr 23.2 622.9 S295V S8T Y93Q S95D D118K A136P S202R W260F N279EL288I L294P 10.5 A & H 46 C. 16 hr 21.3 616.8 S295V Y93Q S95D D118KA136P S202R G257A W260F N279E L288I 10.5 A & H 46 C. 16 hr 26.3 690.4L294P S295V N45G Y93Q S95D D118K A136P S202R W260F N279E L288I 10.5 A &H 46 C. 16 hr 22.4 527.1 L294P S295V Y93Q S95D D118K A136P S202R R244KW260F N279E L288I 10.5 A & H 46 C. 16 hr 40.8 465.4 L294P S295V Y93QS95D D118K A136P P183G S202R W260F N279E L288I 10.5 A & H 46 C. 16 hr24.7 597.3 L294P S295V Y93Q S95D D118K E133R A136P S202R W260F N279EL288I 10.5 A & H 46 C. 16 hr 23.3 729.6 L294P S295V Y93Q S95D S98P D118KA136P S202R W260F N279E L288I L294P 10.5 A & H 46 C. 16 hr 27.1 332.1S295V Y93Q S95D I114Q D118K A136P S202R W260F N279E L288I 10.5 A & H 46C. 16 hr 33.0 497.5 L294P S295V Y93Q S95D I114W D118K A136P S202R W260FN279E L288I 10.5 A & H 46 C. 16 hr 26.6 585.4 L294P S295V Y93Q S95DD118K A136P S202R W260F A276D N279E L288I 10.5 A & H 46 C. 16 hr 28.2637.9 L294P S295V Y93Q S95D D118K A136P S202R W260F N279E N283W L288I10.5 A & H 46 C. 16 hr 26.4 619.5 L294P S295V D57N Y93Q S95D D118K A136PS202R W260F N279E L288I L294P 10.5 A & H 46 C. 16 hr 20.7 364.0 S295VQ60R Y93Q S95D D118K A136P S202R W260F N279E L288I 10.5 A & H 46 C. 16hr 24.2 1054.9 L294P S295V E77K Y93Q S95D D118K A136P S202R W260F N279EL288I L294P 10.5 A & H 46 C. 16 hr 23.5 448.5 S295V Y93Q S95D D118KA136P H172R S202R W260F N279E L288I 10.5 A & H 46 C. 16 hr 22.5 212.8L294P S295V Y93Q S95D D118K A136P S202R A250G W260F N279E L288I 10.5 A &H 46 C. 16 hr 28.7 148.3 L294P S295V Y93Q S95D D118K A136P S202R W260FN279E L288I L294K 10.5 A & H 46 C. 16 hr 41.6 379.1 S295G A1V E77N Y93QD118K A136P D139R S202R R210G W260F L288I 10.5 A & H 46 C. 18 hr 30.5606.4 L294P S295V A1V G47K Y93Q D118K A136P D139R S202R R210G W260FL288I 10.5 A & H 46 C. 18 hr 31.3 696.8 L294P S295V A1V D78G Y93Q D118KA136P D139R S202R R210G W260F L288I 10.5 A & H 46 C. 18 hr 37.4 731.9L294P S295V A1V Y93Q D104G D118K A136P D139R S202R R210G W260F 10.5 A &H 46 C. 18 hr 28.7 698.1 L288I L294P S295V A1V Y93Q S111A D118K A136PD139R S202R R210G W260F 10.5 A & H 46 C. 18 hr 30.8 750.5 L288I L294PS295V A1V Y93Q S111R D118K A136P D139R S202R R210G W260F 10.5 A & H 46C. 18 hr 27.5 720.2 L288I L294P S295V A1V Y93Q D118K A136P D139R K142VS202R R210G W260F 10.5 A & H 46 C. 18 hr 37.6 783.8 L288I L294P S295VA1V R70K Y93Q D118K A136P D139R S202R R210G W260F L288I 10.5 A & H 46 C.18 hr 28.1 721.1 L294P S295V A1V N18V Y93Q D118K A136P D139R S202R R210GW260F L288I 10.5 A & H 46 C. 18 hr 27.8 866.2 L294P S295V A1V N18R Y93QD118K A136P D139R S202R R210G W260F L288I 10.5 A & H 46 C. 18 hr 32.7555.3 L294P S295V A1V Y93Q D118K A136P D139R Y174R S202R R210G W260F10.5 A & H 46 C. 18 hr 37.1 347.8 L288I L294P S295V A1V Y93Q D118K A136PD139R Q169R S202R R210G W260F 10.5 A & H 46 C. 18 hr 30.4 783.5 L288IL294P S295V A1V Y93Q D118K A136P D139R E177Y S202R R210G W260F 10.5 A &H 46 C. 18 hr 30.3 808.2 L288I L294P S295V A1V Y93Q D118K A136P D139RN150R S202R R210G W260F 10.5 A & H 46 C. 18 hr 22.1 981.4 L288I L294PS295V A1V Y93Q D118K A136P D139R R185G S202R R210G W260F 10.5 A & H 46C. 18 hr 30.6 723.8 L288I L294P S295V A1V Y93Q D118K A136P D139R S202RR210G E234F W260F 10.5 A & H 46 C. 18 hr 32.2 803.1 L288I L294P S295VA1V Y93Q D118K A136P D139R S202R R210G A235R W260F 10.5 A & H 46 C. 18hr 34.0 703.5 L288I L294P S295V A1V Y93Q D118K A136P D139R S202R R210GA235K W260F 10.5 A & H 46 C. 18 hr 20.5 659.2 L288I L294P S295V A1V Y93QS95D D118K A136P D139R S202R R210G W260F L288I 10.5 A & H 46 C. 18 hr29.8 359.5 L294P S295V A1V Y93Q A97R D118K A136P D139R S202R R210G W260FL288I 10.5 A & H 46 C. 18 hr 29.5 451.3 L294P S295V A1V Y93Q A97S D118KA136P D139R S202R R210G W260F L288I 10.5 A & H 46 C. 18 hr 29.1 602.0L294P S295V A1V Y93Q D118K T119R A136P D139R S202R R210G W260F 10.5 A &H 46 C. 18 hr 23.5 560.5 L288I L294P S295V A1V Y93Q D118K A136P D139RN200T S202R R210G W260F 10.5 A & H 46 C. 18 hr 25.8 855.3 L288I L294PS295V A1V Y93Q N100Y D118K A136P D139R S202R R210G W260F 10.5 A & H 46C. 18 hr 27.0 560.6 L288I L294P S295V A1V Y93Q N100H D118K A136P D139RS202R R210G W260F 10.5 A & H 46 C. 18 hr 28.4 573.3 L288I L294P S295VA1V Y93Q D118K A136P D139R S202R R210G W260F N273D 10.5 A & H 46 C. 18hr 30.2 632.7 L288I L294P S295V A1V Y93Q D118K A136P D139R S202R R210GW260F N273E 10.5 A & H 46 C. 18 hr 25.7 676.5 L288I L294P S295V A1V Y6HY93Q D118K A136P D139R S202R R210G W260F L288I 10.5 A & H 46 C. 18 hr21.3 613.7 L294P S295V A1V Y6M Y93Q D118K A136P D139R S202R R210G W260FL288I 10.5 A & H 46 C. 18 hr 36.2 739.7 L294P S295V A1V Y93Q D118K A136PD139R P183T S202R R210G W260F 10.5 A & H 46 C. 18 hr 32.7 1021.9 L288IL294P S295V A1V Y93Q D118K A136P D139R S202R R210G W260F N272M 10.5 A &H 46 C. 18 hr 35.9 603.2 L288I L294P S295V A1V Y93Q D118K A136P D139RS202R R210G W260F N272T 10.5 A & H 46 C. 18 hr 34.5 896.9 L288I L294PS295V A1V Y93Q D118K A136P D139R S202R R210G W260F N283H 10.5 A & H 46C. 18 hr 33.2 919.7 L288I L294P S295V A1V Y93Q D118K A136P D139R S202RR210G W260F A276W 10.5 A & H 46 C. 18 hr 29.5 669.4 L288I L294P S295VA1V T11K Y93Q D118K A136P D139R S202R R210G W260F L288I 10.5 A & H 46 C.18 hr 31.6 686.3 L294P S295V A1V T11R Y93Q D118K A136P D139R S202R R210GW260F L288I 10.5 A & H 46 C. 18 hr 26.5 592.8 L294P S295V A1V A30T Y93QD118K A136P D139R S202R R210G G257A 10.5 A & H 46 C. 18 hr 24.3 1569.3W260F A276D L288I L294P S295V A1V D34G Y93Q D118K A136P D139R S202RR210G W260F L288I 10.5 A & H 46 C. 18 hr 28.4 243.5 L294P S295V A1V Y93QD118K A136P D139R S202R R210G W260F L288I 10.5 A & H 46 C. 18 hr 23.1754.0 L294P S295V Y93Q S95D D118K A136P D139R S202R R210G Q243Y W260F10.5 A & H 46 C. 18 hr 36.0 1188.3 L288I L294P S295V Y93Q S95D D118KA136P D139R S202R R210G Q243K W260F 10.5 A & H 46 C. 18 hr 26.7 1413.3L288I L294P S295V Y93Q S95D D118K A136P D139R S202R R210G Q243H W260F10.5 A & H 46 C. 18 hr 27.1 942.0 L288I L294P S295V S3P Y93Q S95D D118KA136P D139R S202R R210G W260F L288I 10.5 A & H 46 C. 18 hr 30.4 979.8L294P S295V G47A Y93Q S95D D118K A136P D139R S202R R210G W260F 10.5 A &H 46 C. 18 hr 27.2 727.1 L288I L294P S295V E77T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.5 A & H 46 C. 18 hr 25.5 745.6 L288I L294PS295V G47S Y93Q S95D D118K A136P D139R S202R R210G W260F 10.5 A & H 46C. 18 hr 26.1 688.9 L288I L294P S295V H80K Y93Q S95D D118K A136P D139RS202R R210G W260F 10.5 A & H 46 C. 18 hr 27.8 959.2 L288I L294P S295VY93Q S95D D118K A136P D139R S202R R210G W260F A276E 10.5 A & H 46 C. 18hr 45.0 1602.2 L288I L294P S295V G59Q Y93Q S95D D118K A136P D139R S202RR210G W260F 10.5 A & H 46 C. 18 hr 28.0 450.6 L288I L294P S295V Y93QS95D D118K A136P D139R S202R R210G G257A W260F 10.5 A & H 46 C. 18 hr39.4 1331.9 L288I L294P S295V A83S Y93Q S95D D118K A136P D139R S202RR210G W260F 10.5 A & H 46 C. 18 hr 42.0 940.2 L288I L294P S295V E77NY93Q S95D D118K A136P D139R S202R R210G W260F 10.5 A & H 46 C. 18 hr41.0 884.5 L288I L294P S295V G47K Y93Q S95D D118K A136P D139R S202RR210G W260F 10.5 A & H 46 C. 18 hr 27.0 888.5 L288I L294P S295V H80RY93Q S95D D118K A136P D139R S202R R210G W260F 10.5 A & H 46 C. 18 hr41.6 1061.2 L288I L294P S295V D78G Y93Q S95D D118K A136P D139R S202RR210G W260F 10.5 A & H 46 C. 18 hr 27.4 1119.2 L288I L294P S295V E41VY93Q S95D D118K A136P D139R S202R R210G W260F 10.5 A & H 46 C. 18 hr21.1 1062.5 L288I L294P S295V Y93Q S95D D104A D118K A136P D139R S202RR210G W260F 10.5 A & H 46 C. 18 hr 54.4 765.2 L288I L294P S295V Y93QS95D S111K D118K A136P D139R S202R R210G W260F 10.5 A & H 46 C. 18 hr34.2 847.6 L288I L294P S295V Y93Q S95D D118K A136P D139R K142M S202RR210G W260F 10.5 A & H 46 C. 18 hr 32.2 1104.7 L288I L294P S295V Y93QS95D D118K A136P D139R K142V S202R R210G W260F 10.5 A & H 46 C. 18 hr49.3 1107.1 L288I L294P S295V D65E Y93Q S95D D118K A136P D139R S202RR210G W260F 10.5 A & H 46 C. 18 hr 48.0 730.8 L288I L294P S295V R70KY93Q S95D D118K A136P D139R S202R R210G W260F 10.5 A & H 46 C. 18 hr50.3 959.4 L288I L294P S295V N45G Y93Q S95D D118K A136P D139R S202RR210G W260F 10.5 A & H 46 C. 18 hr 36.8 889.8 L288I L294P S295V Q35LY93Q S95D D118K A136P D139R S202R R210G W260F 10.5 A & H 46 C. 18 hr35.8 638.2 L288I L294P S295V N18V Y93Q S95D D118K A136P D139R S202RR210G W260F 10.5 A & H 46 C. 18 hr 42.6 1161.8 L288I L294P S295V N18RY93Q S95D D118K A136P D139R S202R R210G W260F 10.5 A & H 46 C. 18 hr27.1 805.5 L288I L294P S295V N71S Y93Q S95D D118K A136P D139R S202RR210G W260F 10.5 A & H 46 C. 18 hr 24.8 758.3 L288I L294P S295V Y93QS95D D118K A136P D139R Y174R S202R R210G W260F 10.5 A & H 46 C. 18 hr28.6 549.1 L288I L294P S295V Y93Q S95D D118K A136P D139R Y174L S202RR210G W260F 10.5 A & H 46 C. 18 hr 26.5 733.0 L288I L294P S295V Y93QS95D D118K A136P D139R Q143R S202R R210G W260F 10.5 A & H 46 C. 18 hr37.1 650.0 L288I L294P S295V Y93Q S95D D118K A136P D139R N180R S202RR210G W260F 10.5 A & H 46 C. 18 hr 31.9 917.9 L288I L294P S295V Y93QS95D D118K A136P D139R Q169A S202R R210G W260F 10.5 A & H 46 C. 18 hr58.2 1004.4 L288I L294P S295V Y93Q S95D D118K A136P D139R Q169K S202RR210G W260F 10.5 A & H 46 C. 18 hr 47.2 184.0 L288I L294P S295V Y93QS95D D118K A136P D139R E177S S202R R210G W260F 10.5 A & H 46 C. 18 hr33.9 1050.2 L288I L294P S295V Y93Q S95D D118K A136P D139R E177Y S202RR210G W260F 10.5 A & H 46 C. 18 hr 35.0 1054.1 L288I L294P S295V Y93QS95D D118K A136P D139R N150T S202R R210G W260F 10.5 A & H 46 C. 18 hr34.0 1347.2 L288I L294P S295V Y93Q S95D D118K A136P D139R N150S S202RR210G W260F 10.5 A & H 46 C. 18 hr 42.6 218.8 L288I L294P S295V Y93QS95D D118K A136P D139R N150R S202R R210G W260F 10.5 A & H 46 C. 18 hr41.6 973.6 L288I L294P S295V Y93Q S95D D118K A136P D139R Q184K S202RR210G W260F 10.5 A & H 46 C. 18 hr 42.4 1003.1 L288I L294P S295V Y93QS95D D118K A136P D139R Q184S S202R R210G W260F 10.5 A & H 46 C. 18 hr30.0 780.7 L288I L294P S295V Y93Q S95D D118K A136P D139R R185G S202RR210G W260F 10.5 A & H 46 C. 18 hr 29.0 863.4 L288I L294P S295V Y93QS95D D118K A136P D139R S202R R210G E234F W260F 10.5 A & H 46 C. 18 hr38.3 1148.4 L288I L294P S295V Y93Q S95D D118K A136P D139R S202R R210GA235R W260F 10.5 A & H 46 C. 18 hr 33.8 784.6 L288I L294P S295V Y93QS95D D118K A136P D139R S202R R210G R244K W260F 10.5 A & H 46 C. 18 hr35.6 958.0 L288I L294P S295V Y93Q S95D K116R D118K A136P D139R S202RR210G W260F 10.5 A & H 46 C. 18 hr 41.9 837.9 L288I L294P S295V Y93QS95D D118K T119R A136P D139R S202R R210G W260F 10.5 A & H 46 C. 18 hr40.1 725.0 L288I L294P S295V Y93Q S95D D118K A136P D139R N200T S202RR210G W260F 10.5 A & H 46 C. 18 hr 23.5 1089.3 L288I L294P S295V Y93QS95D D118K A136P D139R S202R R205K R210G W260F 10.5 A & H 46 C. 18 hr29.5 786.2 L288I L294P S295V Y93Q S95D D118K A136P D139R S202R R210GW260F N279D 10.5 A & H 46 C. 18 hr 39.1 1109.3 L288I L294P S295V Y93QS95D N100Y D118K A136P D139R S202R R210G W260F 10.5 A & H 46 C. 18 hr33.7 816.5 L288I L294P S295V Y93Q S95D N100H D118K A136P D139R S202RR210G W260F 10.5 A & H 46 C. 18 hr 26.7 694.8 L288I L294P S295V Y93QS95D D118K A136P D139R S202R R210G W260F N273E 10.5 A & H 46 C. 18 hr45.1 1174.7 L288I L294P S295V Y6H Y93Q S95D D118K A136P D139R S202RR210G W260F L288I 10.5 A & H 46 C. 18 hr 31.7 865.6 L294P S295V Y6M Y93QS95D D118K A136P D139R S202R R210G W260F L288I 10.5 A & H 46 C. 18 hr28.1 848.4 L294P S295V Y93Q S95D D118K A136P D139R S202R R210G W260FN272M 10.5 A & H 46 C. 18 hr 33.2 761.8 L288I L294P S295V Y93Q S95DD118K A136P D139R S202R R210G W260F N272T 10.5 A & H 46 C. 18 hr 22.01159.9 L288I L294P S295V Y93Q S95D D118K A136P D139R S202R R210G W260FN283W 10.5 A & H 46 C. 18 hr 27.0 992.9 L288I L294P S295V Y93Q S95DD118K A136P D139R S202R R210G W260F N283H 10.5 A & H 46 C. 18 hr 25.21452.7 L288I L294P S295V Y93Q S95D D118K A136P D139R S202R R210G W260FA276W 10.5 A & H 46 C. 18 hr 36.9 947.9 L288I L294P S295V Y93Q S95DD118K A136P D139R S202R R210G W260F A276D 10.5 A & H 46 C. 18 hr 38.71210.6 L288I L294P S295V Y93Q S95D D118K A136P D139R S202R R210G W260FT280L 10.5 A & H 46 C. 18 hr 36.3 1151.7 L288I L294P S295V A30T Y93QS95D D118K A136P D139R S202R R210G W260F 10.5 A & H 46 C. 18 hr 42.02171.5 L288I L294P S295V D34G Y93Q S95D D118K A136P D139R S202R R210GW260F 10.5 A & H 46 C. 18 hr 43.5 279.2 L288I L294P S295V D57N Y93Q S95DD118K A136P D139R S202R R210G W260F 10.5 A & H 46 C. 18 hr 48.8 715.2L288I L294P S295V E77K Y93Q S95D D118K A136P D139R S202R R210G W260F10.5 A & H 46 C. 18 hr 38.1 676.6 L288I L294P S295V Y93Q S95D E108SD118K A136P D139R S202R R210G W260F 10.5 A & H 46 C. 18 hr 39.5 496.7L288I L294P S295V Y93Q S95D D118K A136P D139R H172R S202R R210G W260F10.5 A & H 46 C. 18 hr 31.3 638.6 L288I L294P S295V Y93Q S95D D118KA136P D139R S202R R210G T228S W260F 10.5 A & H 46 C. 18 hr 35.8 610.2L288I L294P S295V A1V Q60R Y93Q D118K A136P D139R S202R R210G W260FL288I 10.5 A & H 46 C. 18 hr 25.3 1039.2 L294P S295V A1V Y93Q S98T D118KA136P D139R S202R R210G W260F L288I 10.5 A & H 46 C. 18 hr 35.3 487.6L294P S295V A1V Y93Q D118K A136P D139R H172R S202R R210G W260F 10.5 A &H 46 C. 18 hr 29.0 356.2 L288I L294P S295V A1V Y93Q D118K A136P D139RS202R R210G W260F L288I 10.5 A & H 46 C. 18 hr 44.6 222.0 L294G S295RA1V Y93Q I114M D118K A136P D139R S202R R210G W260F L288I 10.5 A & H 46C. 18 hr 33.3 625.0 L294P S295V A1V Y93Q I114W D118K A136P D139R S202RR210G W260F 10.5 A & H 46 C. 18 hr 43.1 655.4 L288I L294P S295V Y93QS95D D118K A136P D139R S202R R210G A250G W260F 10.5 A & H 46 C. 18 hr32.2 155.0 L288I L294P S295V Y93Q S95D D118K A136P D139R S202R R210GK254Y W260F 10.5 A & H 46 C. 18 hr 35.2 424.1 L288I L294P S295V Y93QS95D D118K A136P D139R S202R R210G W260F D268N 10.5 A & H 46 C. 18 hr31.2 214.9 L288I L294P S295V Y93Q S95D D118K A136P D139R S202R R210GW260F A270D 10.5 A & H 46 C. 18 hr 48.4 487.5 L288I L294P S295V Y93QS95D D118K A136P D139R S202R R210G W260F A270N 10.5 A & H 46 C. 18 hr42.2 482.4 L288I L294P S295V Y93Q S95D D118K A136P D139R S202R R210GW260F L288I 10.5 A & H 46 C. 18 hr 50.4 479.8 L294P S295G Y93Q S95D A97RD118K A136P D139R S202R R210G W260F 10.5 A & H 46 C. 18 hr 39.3 544.0L288I L294P S295V Y93Q S95D A97S D118K A136P D139R S202R R210G W260F10.5 A & H 46 C. 18 hr 46.2 583.9 L288I L294P S295V Y93Q S95D I114MD118K A136P D139R S202R R210G W260F 10.5 A & H 46 C. 18 hr 46.3 895.9L288I L294P S295V Y93Q S95D S98T D118K A136P D139R S202R R210G W260F10.5 A & H 46 C. 18 hr 27.5 632.9 L288I L294P S295V Y93Q S95D S98D D118KA136P D139R S202R R210G W260F 10.5 A & H 46 C. 18 hr 64.5 814.6 L288IL294P S295V Y93Q S95D D118K A136P D139R S202R R210G W260F L288I 10.5 A &H 46 C. 18 hr 31.5 609.5 E290A L294P S295V Y93Q S95D D118K A136P D139RS202R R210G W260F L288I 10.5 A & H 46 C. 18 hr 61.1 771.7 L294P S295VT296S Y93Q S95D D118K A136P D139R S202R R210G W260F L288I 10.5 A & H 46C. 18 hr 24.3 1215.3 L294P S295V F298Y A1V H80K Y93Q S95D A136P D139AS202R E234Y Q243E W260F 10.5 A & H 46 C. 18 hr 39.0 1860.9 A276E N279EL288I L294P S295V H80K Y93Q S95D A136P D139A S202R E234Y Q243E W260F10.5 A & H 46 C. 18 hr 39.2 1938.3 A276E N279E L288I L294P S295V H80KY93Q S95D D118K A136P D139A S202R R210G E234Y 10.5 A & H 46 C. 18 hr41.2 1391.5 Q243E W260F A276E N279E N283W L288I L294P S295V V82I Y93QS95D A136P D139A S202R E234Y A235K Q243E 10.5 A & H 46 C. 36 hr 24.11931.1 W260F A276E N279E L288I L294P S295V G47K Y93Q S95D A136P D139AS202R E234Y A235K Q243E 10.5 A & H 46 C. 36 hr 30.0 1650.9 W260F A276EN279E L288I L294P S295V Y93Q S95D A136P D139A S202R N213D E234Y A235KQ243E 10.5 A & H 46 C. 36 hr 29.5 2751.4 W260F A276E N279E L288I L294PS295V Y93Q S95D D118K A136P D139A S202R E234Y A235K Q243E 10.5 A & H 46C. 36 hr 25.5 2411.7 W260F A276E N279E L288I L294P S295V D14S Y93Q S95DA136P D139A S202R E234Y A235K Q243E 10.5 A & H 46 C. 36 hr 28.3 669.1W260F A276E N279E L288I L294P S295V Y93Q S95D I114W A136P D139A S202RE234Y A235K Q243E 10.5 A & H 46 C. 36 hr 20.3 2132.1 W260F A276E N279EL288I L294P S295V D65E Y93Q S95D A136P D139A S202R E234Y A235K Q243E10.5 A & H 46 C. 36 hr 22.6 1787.1 W260F A276E N279E L288I L294P S295VR70K Y93Q S95D A136P D139A S202R E234Y A235K Q243E 10.5 A & H 46 C. 36hr 37.7 2373.2 W260F A276E N279E L288I L294P S295V N45G Y93Q S95D A136PD139A S202R E234Y A235K Q243E 10.5 A & H 46 C. 36 hr 35.3 1986.2 W260FA276E N279E L288I L294P S295V Q35L Y93Q S95D A136P D139A S202R E234YA235K Q243E 10.5 A & H 46 C. 36 hr 23.5 1624.7 W260F A276E N279E L288IL294P S295V N71S Y93Q S95D A136P D139A S202R E234Y A235K Q243E 10.5 A &H 46 C. 36 hr 35.1 2048.6 W260F A276E N279E L288I L294P S295V Y93Q S95DA136P D139A Y174R S202R E234Y A235K Q243E 10.5 A & H 46 C. 36 hr 25.51920.2 W260F A276E N279E L288I L294P S295V Y93Q S95D A136P D139A Y174LS202R E234Y A235K Q243E 10.5 A & H 46 C. 36 hr 34.6 1930.2 W260F A276EN279E L288I L294P S295V Y93Q S95D A136P D139A Q169A S202R E234Y A235KQ243E 10.5 A & H 46 C. 36 hr 22.6 2268.5 W260F A276E N279E L288I L294PS295V Y93Q S95D A136P D139A Q169R S202R E234Y A235K Q243E 10.5 A & H 46C. 36 hr 34.6 2362.8 W260F A276E N279E L288I L294P S295V Y93Q S95D A136PD139A E177Y S202R E234Y A235K Q243E 10.5 A & H 46 C. 36 hr 45.0 1496.0W260F A276E N279E L288I L294P S295V Y93Q S95D A136P D139A N150T S202RE234Y A235K Q243E 10.5 A & H 46 C. 36 hr 29.1 2514.6 W260F A276E N279EL288I L294P S295V Y93Q S95D A136P D139A Q184S S202R E234Y A235K Q243E10.5 A & H 46 C. 36 hr 33.3 2098.2 W260F A276E N279E L288I L294P S295VY93Q S95D A136P D139A R185G S202R E234Y A235K Q243E 10.5 A & H 46 C. 36hr 32.7 2208.0 W260F A276E N279E L288I L294P S295V Y93Q S95D A136P D139AS202R R210G E234Y A235K Q243E 10.5 A & H 46 C. 36 hr 61.3 2662.8 W260FA276E N279E L288I L294P S295V Y93Q S95D A136P D139A N200T S202R E234YA235K Q243E 10.5 A & H 46 C. 36 hr 64.5 2804.2 W260F A276E N279E L288IL294P S295V Y93Q S95D N100Y A136P D139A S202R E234Y A235K Q243E 10.5 A &H 46 C. 36 hr 53.9 1806.1 W260F A276E N279E L288I L294P S295V Y93Q S95DA136P D139A S202R N213V E234Y A235K Q243E 10.5 A & H 46 C. 36 hr 41.02449.3 W260F A276E N279E L288I L294P S295V Y93Q S95D A136P D139A P183GS202R E234Y A235K Q243E 10.5 A & H 46 C. 36 hr 37.7 2389.4 W260F A276EN279E L288I L294P S295V T11K Y93Q S95D A136P D139A S202R E234Y A235KQ243E 10.5 A & H 46 C. 36 hr 29.1 1731.3 W260F A276E N279E L288I L294PS295V T11R Y93Q S95D A136P D139A S202R E234Y A235K Q243E 10.5 A & H 46C. 36 hr 30.5 1712.3 W260F A276E N279E L288I L294P S295V A30T Y93Q S95DA136P D139A S202R E234Y A235K Q243E 10.5 A & H 46 C. 36 hr 59.1 3980.4W260F A276E N279E L288I L294P S295V E77K Y93Q S95D A136P D139A S202RE234Y A235K Q243E 10.5 A & H 46 C. 36 hr 27.8 1673.3 W260F A276E N279EL288I L294P S295V Y93Q S95D A136P D139A S202R T228S E234Y A235K Q243E10.5 A & H 46 C. 36 hr 26.0 1497.7 W260F A276E N279E L288I L294P S295VY93Q S95D A136P D139A S202R N229D E234Y A235K Q243E 10.5 A & H 46 C. 36hr 34.5 2063.4 W260F A276E N279E L288I L294P S295V Y93Q S95D A136P D139AS202R E234Y A235K Q243E W260F 10.5 A & H 46 C. 36 hr 34.4 2040.6 S266AA276E N279E L288I L294P S295V Y93Q S95D A136P D139A S202R E234Y A235KQ243E W260F 10.5 A & H 46 C. 36 hr 36.6 1865.5 A276E N279E L288I L294PS295V F298Y Y93Q S95D A97R A136P D139A S202R E234Y A235K Q243E 10.5 A &H 46 C. 36 hr 23.2 1482.5 W260F A276E N279E L288I L294P S295V Y93Q S95DS98D A136P D139A S202R E234Y A235K Q243E 10.5 A & H 46 C. 36 hr 34.21951.9 W260F A276E N279E L288I L294P S295V Y93Q S95D A136P D139A S202RQ203T E234Y A235K Q243E 10.5 A & H 46 C. 36 hr 38.0 2071.4 W260F A276EN279E L288I L294P S295V Y93Q S95D A136P D139A S202R E234Y A235K Q243EW260F 10.5 A & H 46 C. 36 hr 31.3 1784.6 A276E N279E L288I L294R S295VY93Q S95D K116R D118K A136P D139A S202R E234Y A235K 10.5 A & H 46 C. 36hr 25.4 1518.6 Q243E W260F A276E N279E N283W L288I L294P S295V H80K Y93QS95D D118K A136P D139A S202R E234Y A235K 10.5 A & H 46 C. 36 hr 35.71975.4 Q243E W260F A276E N279E N283W L288I L294P S295V A1G Y93Q S95DD118K A136P D139A S202R E234Y A235K Q243E 10.5 A & H 46 C. 36 hr 43.02568.6 W260F A276E N279E N283W L288I L294P S295V S3P Y93Q S95D D118KA136P D139A S202R E234Y A235K Q243E 10.5 A & H 46 C. 36 hr 42.2 2368.1W260F A276E N279E N283W L288I L294P S295V T37P Y93Q S95D D118K A136PD139A S202R E234Y A235K 10.5 A & H 46 C. 36 hr 38.3 2099.4 Q243E W260FA276E N279E N283W L288I L294P S295V G47A Y93Q S95D D118K A136P D139AS202R E234Y A235K 10.5 A & H 46 C. 36 hr 26.8 1571.6 Q243E W260F A276EN279E N283W L288I L294P S295V V82I Y93Q S95D D118K A136P D139A S202RE234Y A235K Q243E 10.5 A & H 46 C. 36 hr 37.1 2108.7 W260F A276E N279EN283W L288I L294P S295V Y93Q S95D D118K A136P D139A S202R E234Y A235KQ243E 10.5 A & H 46 C. 36 hr 48.6 3017.4 G257A W260F A276E N279E N283WL288I L294P S295V A83S Y93Q S95D D118K A136P D139A S202R E234Y A235K10.5 A & H 46 C. 36 hr 46.3 2758.1 Q243E W260F A276E N279E N283W L288IL294P S295V E77N Y93Q S95D D118K A136P D139A S202R E234Y A235K 10.5 A &H 46 C. 36 hr 41.1 2325.3 Q243E W260F A276E N279E N283W L288I L294PS295V G47K Y93Q S95D D118K A136P D139A S202R E234Y A235K 10.5 A & H 46C. 36 hr 30.2 1708.9 Q243E W260F A276E N279E N283W L288I L294P S295VE41V Y93Q S95D D118K A136P D139A S202R E234Y A235K 10.5 A & H 46 C. 36hr 44.3 2548.3 Q243E W260F A276E N279E N283W L288I L294P S295V Y93Q S95DD104A D118K A136P D139A S202R E234Y A235K 10.5 A & H 46 C. 36 hr 35.52170.8 Q243E W260F A276E N279E N283W L288I L294P S295V Y93Q S95D S111AD118K A136P D139A S202R E234Y A235K 10.5 A & H 46 C. 36 hr 37.9 2086.0Q243E W260F A276E N279E N283W L288I L294P S295V Y93Q S95D S111R D118KA136P D139A S202R E234Y A235K 10.5 A & H 46 C. 36 hr 31.3 1743.2 Q243EW260F A276E N279E N283W L288I L294P S295V Y93Q S95D S111K D118K A136PD139A S202R E234Y A235K 10.5 A & H 46 C. 36 hr 44.7 2515.3 Q243E W260FA276E N279E N283W L288I L294P S295V Y93Q S95D I114M D118K A136P D139AS202R E234Y A235K 10.5 A & H 46 C. 36 hr 43.0 2592.0 Q243E W260F A276EN279E N283W L288I L294P S295V D65E Y93Q S95D D118K A136P D139A S202RE234Y A235K 10.5 A & H 46 C. 36 hr 29.2 1714.4 Q243E W260F A276E N279EN283W L288I L294P S295V T37R Y93Q S95D D118K A136P D139A S202R E234YA235K 10.5 A & H 46 C. 36 hr 45.4 2640.3 Q243E W260F A276E N279E N283WL288I L294P S295V N45G Y93Q S95D D118K A136P D139A S202R E234Y A235K10.5 A & H 46 C. 36 hr 34.0 1949.0 Q243E W260F A276E N279E N283W L288IL294P S295V Q35L Y93Q S95D D118K A136P D139A S202R E234Y A235K 10.5 A &H 46 C. 36 hr 24.0 1446.6 Q243E W260F A276E N279E N283W L288I L294PS295V N18V Y93Q S95D D118K A136P D139A S202R E234Y A235K 10.5 A & H 46C. 36 hr 35.6 1914.8 Q243E W260F A276E N279E N283W L288I L294P S295VS74K Y93Q S95D D118K A136P D139A S202R E234Y A235K 10.5 A & H 46 C. 36hr 41.7 2273.1 Q243E W260F A276E N279E N283W L288I L294P S295V Y93Q S95DD118K A136P D139A Y174L S202R E234Y A235K 10.5 A & H 46 C. 36 hr 39.22131.7 Q243E W260F A276E N279E N283W L288I L294P S295V Y93Q S95D D118KA136P D139A N180R S202R E234Y A235K 10.5 A & H 46 C. 36 hr 32.0 1824.0Q243E W260F A276E N279E N283W L288I L294P S295V Y93Q S95D D118K A136PD139A Q169R S202R E234Y A235K 10.5 A & H 46 C. 36 hr 47.3 2666.4 Q243EW260F A276E N279E N283W L288I L294P S295V Y93Q S95D D118K A136P D139AQ169K S202R E234Y A235K 10.5 A & H 46 C. 36 hr 40.1 2342.9 Q243E W260FA276E N279E N283W L288I L294P S295V Y93Q S95D D118K A136P D139A E177SS202R E234Y A235K 10.5 A & H 46 C. 36 hr 40.1 2020.2 Q243E W260F A276EN279E N283W L288I L294P S295V Y93Q S95D D118K A136P D139A E177Y S202RE234Y A235K 10.5 A & H 46 C. 36 hr 37.3 2129.8 Q243E W260F A276E N279EN283W L288I L294P S295V Y93Q S95D D118K A136P D139A N150S S202R E234YA235K 10.5 A & H 46 C. 36 hr 43.0 2479.7 Q243E W260F A276E N279E N283WL288I L294P S295V Y93Q S95D D118K A136P D139A N150R S202R E234Y A235K10.5 A & H 46 C. 36 hr 43.4 2668.9 Q243E W260F A276E N279E N283W L288IL294P S295V Y93Q S95D D118K A136P D139A Q184E S202R E234Y A235K 10.5 A &H 46 C. 36 hr 37.2 2182.6 Q243E W260F A276E N279E N283W L288I L294PS295V Y93Q S95D D118K A136P D139A Q184K S202R E234Y A235K 10.5 A & H 46C. 36 hr 33.7 1892.4 Q243E W260F A276E N279E N283W L288I L294P S295VY93Q S95D D118K A136P D139A Q184S S202R E234Y A235K 10.5 A & H 46 C. 36hr 35.5 1914.8 Q243E W260F A276E N279E N283W L288I L294P S295V Y93Q S95DD118K A136P D139A R185G S202R E234Y A235K 10.5 A & H 46 C. 36 hr 45.42639.1 Q243E W260F A276E N279E N283W L288I L294P S295V Y93Q S95D D118KA136P D139A S202R R210L E234Y A235K 10.5 A & H 46 C. 36 hr 38.1 2115.9Q243E W260F A276E N279E N283W L288I L294P S295V Y93Q S95D D118K A136PD139A S202R R210M E234Y A235K 10.5 A & H 46 C. 36 hr 44.0 2577.8 Q243EW260F A276E N279E N283W L288I L294P S295V Y93Q S95D D118K A136P D139AS202R R210G E234Y A235K 10.5 A & H 46 C. 36 hr 63.6 4032.0 Q243E W260FA276E N279E N283W L288I L294P S295V Y93Q S95D D118K A136P D139A N200TS202R E234Y A235K 10.5 A & H 46 C. 36 hr 54.8 3483.1 Q243E W260F A276EN279E N283W L288I L294P S295V Y93Q S95D D118K A136P D139A S202R R205KE234Y A235K 10.5 A & H 46 C. 36 hr 32.6 1696.3 Q243E W260F A276E N279EN283W L288I L294P S295V Y93Q S95D N100Y D118K A136P D139A S202R E234YA235K 10.5 A & H 46 C. 36 hr 38.2 1933.7 Q243E W260F A276E N279E N283WL288I L294P S295V Y93Q S95D N100H D118K A136P D139A S202R E234Y A235K10.5 A & H 46 C. 36 hr 33.3 1741.8 Q243E W260F A276E N279E N283W L288IL294P S295V Y6H Y93Q S95D D118K A136P D139A S202R E234Y A235K Q243E 10.5A & H 46 C. 36 hr 32.4 1833.1 W260F A276E N279E N283W L288I L294P S295VY6M Y93Q S95D D118K A136P D139A S202R E234Y A235K Q243E 10.5 A & H 46 C.36 hr 35.6 2033.1 W260F A276E N279E N283W L288I L294P S295V Y93Q S95DD118K A136P D139A S202R N213V E234Y A235K 10.5 A & H 46 C. 36 hr 41.82503.0 Q243E W260F A276E N279E N283W L288I L294P S295V Y93Q S95D D118KA136P D139A P183T S202R E234Y A235K 10.5 A & H 46 C. 36 hr 44.1 2828.0Q243E W260F A276E N279E N283W L288I L294P S295V T11K Y93Q S95D D118KA136P D139A S202R E234Y A235K 10.5 A & H 46 C. 36 hr 34.5 1937.8 Q243EW260F A276E N279E N283W L288I L294P S295V T11R Y93Q S95D D118K A136PD139A S202R E234Y A235K 10.5 A & H 46 C. 36 hr 33.2 1914.8 Q243E W260FA276E N279E N283W L288I L294P S295V Y6H A30T Y93Q S95D D118K A136P D139AS202R E234Y A235K 10.5 A & H 46 C. 36 hr 63.7 4543.9 Q243E W260F A276EN279E N283W L288I L294P S295V D57N Y93Q S95D D118K A136P D139A S202RE234Y A235K 10.5 A & H 46 C. 36 hr 32.5 1888.6 Q243E W260F A276E N279EN283W L288I L294P S295V Q60R Y93Q S95D D118K A136P D139A S202R E234YA235K 10.5 A & H 46 C. 36 hr 47.7 2569.7 Q243E W260F A276E N279E N283WL288I L294P S295V Y93Q S95D D118K A136P D139A S202R N229D E234Y A235K10.5 A & H 46 C. 36 hr 33.8 1809.9 Q243E W260F A276E N279E N283W L288IL294P S295V Y93Q S95D D118K A136P D139A S202R E234Y A235K Q243E 10.5 A &H 46 C. 36 hr 37.6 2133.1 W260F S266A A276E N279E N283W L288I L294PS295V Y93Q S95D D118K A136P D139A S202R E234Y A235K Q243E 10.5 A & H 46C. 36 hr 24.1 1452.5 W260F A270D A276E N279E N283W L288I L294P S295VY93Q S95D A97R D118K A136P D139A S202R E234Y A235K 10.5 A & H 46 C. 36hr 21.9 1278.8 Q243E W260F A276E N279E N283W L288I L294P S295V Y93Q S95DA97S D118K A136P D139A S202R E234Y A235K 10.5 A & H 46 C. 36 hr 28.41665.3 Q243E W260F A276E N279E N283W L288I L294P S295V Y93Q S95D S98DD118K A136P D139A S202R E234Y A235K 10.5 A & H 46 C. 36 hr 42.7 2393.8Q243E W260F A276E N279E N283W L288I L294P S295V Y93Q S95D D118K A136PD139A S202R Q203T E234Y A235K 10.5 A & H 46 C. 36 hr 45.5 2633.5 Q243EW260F A276E N279E N283W L288I L294P S295V A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 59.1 2064.6 L288I L294PS295V A1V A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H44 C. 44 hr 58.8 2003.6 L288I L294P S295V Q243E A30T Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 58.1 1994.0 L288IL294P S295V Q243K A30T Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 44 hr 55.7 2105.9 L288I L294P S295V Q243H A30T Y93QS95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 56.11714.3 L288I L294P S295V S3P A30T Y93Q S95D D118K A136P D139R S202RR210G W260F 10.8 A & H 44 C. 44 hr 58.5 1947.0 L288I L294P S295V G47AA30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44hr 61.0 1945.9 L288I L294P S295V S8T A30T Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 44 hr 37.9 664.6 L288I L294P S295VE77T A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C.44 hr 49.5 1107.5 L288I L294P S295V G47S A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 57.9 1704.2 L288I L294PS295V H80K A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H44 C. 44 hr 54.9 1515.8 L288I L294P S295V S131T A30T Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 66.6 1851.9 L288IL294P S295V A276E A30T Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 44 hr 64.4 2237.5 L288I L294P S295V G257A A30T Y93QS95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 57.41945.9 L288I L294P S295V A83S A30T Y93Q S95D D118K A136P D139R S202RR210G W260F 10.8 A & H 44 C. 44 hr 21.2 664.6 L288I L294P S295V D14KA30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44hr 52.0 1107.5 L288I L294P S295V E77N A30T Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 44 hr 52.4 1704.2 L288I L294P S295VG47K A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C.44 hr 27.2 1515.8 L288I L294P S295V D14A A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 32.3 1107.5 L288I L294PS295V D14S A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H44 C. 44 hr 56.8 1704.2 L288I L294P S295V E41V A30T Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 50.4 1515.8 L288IL294P S295V D104A A30T Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 44 hr 49.6 1851.9 L288I L294P S295V S111R A30T Y93QS95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 52.81851.9 L288I L294P S295V S111K A30T Y93Q S95D D118K A136P D139R S202RR210G W260F 10.8 A & H 44 C. 44 hr 61.7 2237.5 L288I L294P S295V T37RA30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44hr 56.0 1702.9 L288I L294P S295V R70K A30T Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 44 hr 53.4 1784.0 L288I L294P S295VN45G A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C.44 hr 50.5 1663.0 L288I L294P S295V N18R A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 47.7 1778.2 L288I L294PS295V Y174R A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 44 hr 54.7 1784.0 L288I L294P S295V N180R A30T Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 61.4 1784.0 L288IL294P S295V Q169R A30T Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 44 hr 55.1 1663.0 L288I L294P S295V Q169A A30T Y93QS95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 56.71778.3 L288I L294P S295V Q169K A30T Y93Q S95D D118K A136P D139R S202RR210G W260F 10.8 A & H 44 C. 44 hr 57.6 1809.0 L288I L294P S295V E177YA30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44hr 57.0 1274.4 L288I L294P S295V N150T A30T Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 44 hr 55.8 1778.3 L288I L294P S295VN150S A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44C. 44 hr 57.8 2126.9 L288I L294P S295V N150R A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 55.0 2200.6 L288I L294PS295V Q184K A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 44 hr 57.6 1809.0 L288I L294P S295V Q184S A30T Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 41.6 1274.4 L288IL294P S295V E234F A30T Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 44 hr 55.7 2023.2 L288I L294P S295V E234Y A30T Y93QS95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 33.72273.7 L288I L294P S295V A235R A30T Y93Q S95D D118K A136P D139R S202RR210G W260F 10.8 A & H 44 C. 44 hr 53.9 1769.2 L288I L294P S295V R244KA30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44hr 56.8 2300.4 L288I L294P S295V K116R A30T Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 44 hr 40.7 1744.8 L288I L294P S295VT119R A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44C. 44 hr 64.1 1312.4 L288I L294P S295V N200T A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 58.6 2126.9 L288I L294PS295V N279D A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 44 hr 61.2 2200.6 L288I L294P S295V N279E A30T Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 47.8 2029.9 L288IL294P S295V N100Y A30T Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 44 hr 50.0 2067.1 L288I L294P S295V N100H A30T Y93QS95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 59.81951.1 L288I L294P S295V N273E A30T Y93Q S95D D118K A136P D139R S202RR210G W260F 10.8 A & H 44 C. 44 hr 57.5 2029.9 L288I L294P S295V Y6HA30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44hr 56.8 2067.1 L288I L294P S295V P183T A30T Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 44 hr 57.8 1847.9 L288I L294P S295VN283W A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44C. 44 hr 57.9 1951.1 L288I L294P S295V N283H A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 62.3 2273.7 L288I L294PS295V A276D A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 44 hr 55.6 1756.0 L288I L294P S295V T280L A30T Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 44.6 1434.8 L288IL294P S295V T11R A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8A & H 44 C. 44 hr 48.5 1921.8 L288I L294P S295V D57N A30T Y93Q S95DD118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 56.3 1769.2L288I L294P S295V Q60R A30T Y93Q S95D D118K A136P D139R S202R R210GW260F 10.8 A & H 44 C. 44 hr 42.0 1258.4 L288I L294P S295V E108S A30TY93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr43.6 1274.4 L288I L294P S295V H172R A30T Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 44 hr 39.0 1309.3 L288I L294P S295VT228S A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44C. 44 hr 58.1 2145.4 L288I L294P S295V N229D A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 55.8 1753.3 L288I L294PS295V N213V A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 44 hr 57.6 2050.3 L288I L294P S295V N213D A30T Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 50.9 1597.7 L288IL294R S295V Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 40 hr 31.2 1994.0 L288I L294P S295V E177Y Q60R Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 23.3 2105.9 L288IL294P S295V E234F Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 40 hr 25.1 1714.3 L288I L294P S295V R205K Q60R Y93QS95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 21.7375.7 L288I L294P S295V Y6M Q60R Y93Q S95D D118K A136P D139R S202R R210GW260F 10.8 A & H 44 C. 40 hr 31.5 1947.0 L288I L294P S295V A1V Q60R Y93QS95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 36.22127.8 L288I L294P S295V Q243Y Q60R Y93Q S95D D118K A136P D139R S202RR210G W260F 10.8 A & H 44 C. 40 hr 40.3 1474.4 L288I L294P S295V Q243KQ60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40hr 36.9 2176.5 L288I L294P S295V S3P Q60R Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 40 hr 38.8 2457.5 L288I L294P S295VS8T Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C.40 hr 28.8 2517.3 L288I L294P S295V E77T Q60R Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 31.8 664.6 L288I L294PS295V H80K Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H44 C. 40 hr 25.3 439.9 L288I L294P S295V S131T Q60R Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 42.8 1767.7 L288IL294P S295V A276E Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 40 hr 26.0 1679.2 L288I L294P S295V V82I Q60R Y93Q S95DD118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 41.7 808.2L288I L294P S295V G257A Q60R Y93Q S95D D118K A136P D139R S202R R210GW260F 10.8 A & H 44 C. 40 hr 35.6 573.8 L288I L294P S295V A83S Q60R Y93QS95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 34.01515.8 L288I L294P S295V E77N Q60R Y93Q S95D D118K A136P D139R S202RR210G W260F 10.8 A & H 44 C. 40 hr 34.8 570.3 L288I L294P S295V H80RQ60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40hr 32.6 1586.9 L288I L294P S295V E41V Q60R Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 40 hr 26.8 1534.8 L288I L294P S295VS111A Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44C. 40 hr 24.3 424.8 L288I L294P S295V S111R Q60R Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 28.4 1784.0 L288I L294PS295V S111K Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 40 hr 23.4 2248.8 L288I L294P S295V D65E Q60R Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 32.4 1663.0 L288IL294P S295V R70K Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8A & H 44 C. 40 hr 27.3 1788.6 L288I L294P S295V N45G Q60R Y93Q S95DD118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 39.1 2188.3L288I L294P S295V N18V Q60R Y93Q S95D D118K A136P D139R S202R R210GW260F 10.8 A & H 44 C. 40 hr 21.6 1778.2 L288I L294P S295V N18R Q60RY93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr25.8 2056.9 L288I L294P S295V N71S Q60R Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 40 hr 22.2 1861.3 L288I L294P S295VY174L Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44C. 40 hr 26.0 1274.4 L288I L294P S295V Q169A Q60R Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 28.3 2023.2 L288I L294PS295V Q169R Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 40 hr 28.1 989.2 L288I L294P S295V Q169K Q60R Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 32.9 1919.7 L288IL294P S295V E177S Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 40 hr 32.2 1930.8 L288I L294P S295V N150T Q60R Y93QS95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 35.31248.0 L288I L294P S295V N150S Q60R Y93Q S95D D118K A136P D139R S202RR210G W260F 10.8 A & H 44 C. 40 hr 29.1 2374.4 L288I L294P S295V N150RQ60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40hr 29.9 504.8 L288I L294P S295V Q184E Q60R Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 40 hr 29.7 2126.9 L288I L294P S295VQ184K Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44C. 40 hr 27.1 2200.6 L288I L294P S295V Q184S Q60R Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 26.8 1393.9 L288I L294PS295V R185G Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 40 hr 24.4 431.2 L288I L294P S295V A235R Q60R Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 27.6 2274.2 L288IL294P S295V A235K Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 40 hr 25.2 2029.9 L288I L294P S295V R244K Q60R Y93QS95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 22.7388.9 L288I L294P S295V K116R Q60R Y93Q S95D D118K A136P D139R S202RR210G W260F 10.8 A & H 44 C. 40 hr 36.0 2067.1 L288I L294P S295V N200TQ60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40hr 35.7 1992.7 L288I L294P S295V N279D Q60R Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 40 hr 48.6 1951.1 L288I L294P S295VN279E Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44C. 40 hr 24.1 2273.7 L288I L294P S295V N100Y Q60R Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 21.2 1894.3 L288I L294PS295V N100H Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 40 hr 37.7 586.6 L288I L294P S295V N273D Q60R Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 32.8 1393.3 L288IL294P S295V N273E Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 40 hr 23.8 1585.1 L288I L294P S295V Y6H Q60R Y93Q S95DD118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 32.4 533.9L288I L294P S295V P183T Q60R Y93Q S95D D118K A136P D139R S202R R210GW260F 10.8 A & H 44 C. 40 hr 37.1 1311.4 L288I L294P S295V N272T Q60RY93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr38.5 1189.7 L288I L294P S295V N283H Q60R Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 40 hr 38.7 619.7 L288I L294P S295VA276D Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44C. 40 hr 34.1 1768.9 L288I L294P S295V T280L Q60R Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 56.9 922.9 L288I L294PS295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H44 C. 40 hr 30.0 500.7 L288I L294P S295V Y93Q S95D D118K A136P D139AK142S S202R E234Y A235K 10.8 A & H 44 C. 40 hr 34.9 375.7 Q243E W260FA276E N279E N283W L288I L294P S295V Y93Q S95D D118K A136P D139A S202RE234Y A235K Q243E 10.8 A & H 44 C. 40 hr 42.4 516.8 R244K W260F A276EN279E N283W L288I L294P S295V Y93Q S95D D118K A136P D139A S202R E234YA235K Q243E 10.8 A & H 44 C. 40 hr 41.0 1091.1 W260F N272T A276E N279EN283W L288I L294P S295V Y93Q S95D D118K A136P D139A S202R E234Y A235KQ243E 10.8 A & H 44 C. 40 hr 42.0 665.9 W260F N273D A276E N279E N283WL288I L294P S295V Y93Q S95D D118K A136P D139A S202R E234Y A235K Q243E10.8 A & H 44 C. 40 hr 42.5 599.1 W260F N273E A276E N279E N283W L288IL294P S295V Y93Q S95D D118K A136P D139A S202R E234Y A235K Q243E 10.8 A &H 44 C. 40 hr 29.6 311.8 W260F A276E N279E T280L N283W L288I L294P S295VS95D D118K A136P D139A S202R E234Y A235K Q243E W260F 10.8 A & H 44 C. 40hr 24.9 603.0 A276E N279E N283W L288I L294P S295V H80K Y93Q S95D D118KA136P D139A S202R R210G A235K 10.8 A & H 44 C. 40 hr 47.4 372.4 Q243EW260F A276E N279E N283W L288I L294P S295V A1V H80K Y93Q S95D D118K A136PD139A S202R E234Y Q243E 10.8 A & H 44 C. 40 hr 36.1 448.8 W260F A276EN279E N283W L288I L294P S295V A1V H80K Y93Q S95D D118K A136P D139R S202RR210G E234Y 10.8 A & H 44 C. 40 hr 32.5 424.8 Q243E W260F A276E N279EN283W L288I L294P S295V Q60R Y93Q S95D D118K A136P D139R S202R R210GW260F 10.8 A & H 44 C. 44 hr 25.4 492.3 L288I L294P S295V S266A Q60RY93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr20.9 395.9 L288I L294P S295V A97R Q60R Y93Q S95D D118K A136P D139R S202RR210G W260F 10.8 A & H 44 C. 44 hr 21.5 394.3 L288I L294P S295V A97SQ60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44hr 28.4 350.8 L288I L294P S295V S98P Q60R Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 44 hr 26.0 453.9 L288I L294P S295VI114M Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44C. 44 hr 29.1 479.5 L288I L294P S295V I114Q Q60R Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 30.6 482.6 L288I L294PS295V I114W Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 44 hr 27.7 522.1 L288I L294P S295V S98D Q60R Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 20.7 525.6 L288IL294P S295V N200D Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 44 hr 27.7 506.6 L288I L294P S295V Q203T Q60R Y93Q S95DD118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 22.1 461.1L288I L294P S295V T296S Q60R Y93Q S95D D118K A136P D139R S202R R210GW260F 10.8 A & H 44 C. 44 hr 27.8 459.5 L288I L294P S295V F298Y Q60RY93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr30.3 502.4 L288I L294P S295V N213V Q60R Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 44 hr 36.8 431.2 L288I L294P S295VN213D Q60R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44C. 44 hr 24.8 451.4 L288I L294R S295V A30T Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 44 hr 51.8 826.4 L288I L294P S295VS266A A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44C. 44 hr 41.0 586.6 L288I L294P S295V A270D A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 27.5 563.3 L288I L294PS295V A270N A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 44 hr 31.9 424.1 L288I L294P S295G A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 31.3 533.9 L288I L294KS295G A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44C. 44 hr 41.9 1165.6 L288I L294P S295V A97R A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 45.9 636.4 L288I L294PS295V A97S A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H44 C. 44 hr 55.2 625.0 L288I L294P S295V S98P A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 59.3 1824.3 L288I L294PS295V I114M A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 44 hr 56.8 619.7 L288I L294P S295V I114Q A30T Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 50.0 360.0 L288IL294P S295V S98T A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8A & H 44 C. 44 hr 54.5 360.7 L288I L294P S295V S98D A30T Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 52.5 1035.5 L288IL294P S295V N200D A30T Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 44 hr 51.1 129.4 L288I L294P S295V Q203T A30T Y93Q S95DD118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr 49.0 1710.6L288I L294P S295V E290A A30T Y93Q S95D D118K A136P D139R S202R R210GW260F 10.8 A & H 44 C. 44 hr 54.1 1908.7 L288I L294P S295V T296S A30TY93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 44 hr60.9 365.6 L288I L294P S295V F298Y T37R Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 40 hr 78.6 524.4 A276E L288I L294PS295V Y93Q S95D D118K A136P D139R S202R R210G Q243K W260F 10.8 A & H 44C. 40 hr 66.4 1026.7 N279E L288I L294P S295V E41V Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 64.4 327.4 A276E L288IL294P S295V A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 40 hr 65.2 275.0 A276E L288I L294P S295V E77T Y93Q S95D D118KA136P D139R S202R R210G Q243K 10.8 A & H 44 C. 40 hr 38.1 244.4 W260FL288I L294P S295V Y6H Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8A & H 44 C. 40 hr 61.8 184.4 A276E L288I L294P S295V H80K Y93Q S95DD118K A136P D139R S202R R210G Q243K 10.8 A & H 44 C. 40 hr 71.3 285.5W260F L288I L294P S295V S3P Y93Q S95D D118K A136P D139R S202R R210GW260F 10.8 A & H 44 C. 40 hr 54.2 439.8 A276E L288I L294P S295V Y93QS95D D118K A136P D139R N150T S202R R210G W260F 10.8 A & H 44 C. 40 hr59.3 509.2 A276E L288I L294P S295V Y93Q S95D D118K A136P D139R S202RR210G Q243K W260F 10.8 A & H 44 C. 40 hr 58.7 502.7 A276E L288I L294PS295V A30T Y93Q S95D D118K A136P D139R S202R R210G Q243K 10.8 A & H 44C. 40 hr 59.2 503.6 W260F L288I L294P S295V Y93Q S95D D118K A136P D139RS202R R210G E234Y Q243K 10.8 A & H 44 C. 40 hr 52.1 783.5 W260F L288IL294P S295V Y93Q S95D I114Q D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 40 hr 42.7 507.7 A276E L288I L294P S295V Y93Q S95D D118K A136PD139R S202R R210G E234Y W260F 10.8 A & H 44 C. 40 hr 58.0 450.0 A276EL288I L294P S295V E77N Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 40 hr 51.6 468.1 A276E L288I L294P S295V Y93Q S95DD118K A136P D139R Y174R S202R R210G W260F 10.8 A & H 44 C. 40 hr 46.9502.4 A276E L288I L294P S295V Y93Q S95D D118K A136P D139R S202R R210GQ243E W260F 10.8 A & H 44 C. 40 hr 50.5 662.6 A276E L288I L294P S295VY93Q S95D D118K A136P D139R S202R R210G Q243H W260F 10.8 A & H 44 C. 40hr 50.0 442.6 A276E L288I L294P S295V Y93Q S95D D118K A136P D139R S202RR210G Q243Y W260F 10.8 A & H 44 C. 40 hr 52.7 475.0 A276E L288I L294PS295V Q60R Y93Q S95D D118K A136P D139R S202R R210G Q243K 10.8 A & H 44C. 40 hr 49.3 478.4 W260F L288I L294P S295V S8T Y93Q S95D D118K A136PD139R S202R R210G Q243K 10.8 A & H 44 C. 40 hr 47.1 2245.4 W260F L288IL294P S295V Y93Q S95D D118K A136P D139R N150T S202R R210G Q243K 10.8 A &H 44 C. 40 hr 48.9 597.5 W260F L288I L294P S295V H80R Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 44.0 589.9 A276EL288I L294P S295V Y93Q S95D D118K A136P D139R S202R R210G Q243K W260F10.8 A & H 44 C. 40 hr 46.5 2235.5 N279D L288I L294P S295V A1G Y93Q S95DD118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 44.6 1312.9A276E L288I L294P S295V Y93Q S95D I114M D118K A136P D139R S202R R210GW260F 10.8 A & H 44 C. 40 hr 33.3 1305.9 A276E L288I L294P S295V Y93QS95D D118K S131T A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr47.2 1690.0 A276E L288I L294P S295V Y93Q S95D D118K A136P D139R S202RR210G W260F A276E 10.8 A & H 44 C. 40 hr 47.8 223.9 N283H L288I L294PS295V Y93Q S95D D118K A136P D139R S202R R210G W260F A276E 10.8 A & H 44C. 40 hr 32.9 915.7 L288I L294P S295V T296S Y93Q S95D D118K A136P D139RS202R R210G W260F A276E 10.8 A & H 44 C. 40 hr 46.6 2326.7 N283W L288IL294P S295V V82I Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 40 hr 39.3 561.1 A276E L288I L294P S295V Y93Q S95D D118K A136PD139R S202R R210G Q243K W260F 10.8 A & H 44 C. 40 hr 49.7 554.6 T280LL288I L294P S295V Y93Q S95D D118K A136P D139R N150R S202R R210G Q243K10.8 A & H 44 C. 40 hr 81.4 1181.8 W260F L288I L294P S295V R70K Y93QS95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 49.5765.9 A276E L288I L294P S295V Y93Q S95D D118K A136P D139R S202R R210GQ243K W260F 10.8 A & H 44 C. 40 hr 43.2 1839.5 A276D L288I L294P S295VY93Q S95D D118K A136P D139R N150S S202R R210G W260F 10.8 A & H 44 C. 40hr 46.8 1681.3 A276E L288I L294P S295V A83S Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 40 hr 45.4 538.1 A276E L288I L294PS295V Y93Q S95D D118K A136P D139R S202R R210G W260F A276E 10.8 A & H 44C. 40 hr 44.4 529.1 N279E L288I L294P S295V Y93Q S95D D118K A136P D139RS202R R210G Q243K W260F 10.8 A & H 44 C. 40 hr 41.3 528.9 N283H L288IL294P S295V S74K Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 40 hr 43.0 1607.3 A276E L288I L294P S295V Y93Q S95D D118K A136PD139R S202R R210G A235R W260F 10.8 A & H 44 C. 40 hr 44.2 2481.6 A276EL288I L294P S295V Y93Q S95D D118K A136P D139R Q169R S202R R210G W260F10.8 A & H 44 C. 40 hr 39.1 509.0 A276E L288I L294P S295V Y93Q S95DD118K A136P D139R S202R R210G W260F A276E 10.8 A & H 44 C. 40 hr 28.11943.2 L288I L294R S295V H80K Y93Q S95D D118K A136P D139R S202R R210GW260F 10.8 A & H 44 C. 40 hr 41.8 501.7 A276E L288I L294P S295V Y93QS95D D118K A136P D139R P183T S202R R210G Q243K 10.8 A & H 44 C. 40 hr44.8 498.4 W260F L288I L294P S295V G47K Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 40 hr 38.2 1768.4 A276E L288I L294PS295V Y93Q S95D D118K A136P D139R N180R S202R R210G W260F 10.8 A & H 44C. 40 hr 39.2 2087.6 A276E L288I L294P S295V A83S Y93Q S95D D118K A136PD139R S202R R210G Q243K 10.8 A & H 44 C. 40 hr 39.7 489.0 W260F L288IL294P S295V Y93Q S95D D118K A136P D139R P183G S202R R210G Q243K 10.8 A &H 44 C. 40 hr 50.1 165.7 W260F L288I L294P S295V H80R Y93Q S95D D118KA136P D139R S202R R210G Q243K 10.8 A & H 44 C. 40 hr 45.4 341.3 W260FL288I L294P S295V Y93Q S95D D118K A136P D139R E177Y S202R R210G Q243K10.8 A & H 44 C. 40 hr 39.3 1213.0 W260F L288I L294P S295V S8T Y93Q S95DD118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 38.9 820.5A276E L288I L294P S295V Y93Q S95D D118K A136P D139R S202R Q203T R210GQ243K 10.8 A & H 44 C. 40 hr 32.6 920.2 W260F L288I L294P S295V Y6M Y93QS95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 43.8516.9 A276E L288I L294P S295V E41V Y93Q S95D D118K A136P D139R S202RR210G Q243K 10.8 A & H 44 C. 40 hr 42.1 899.6 W260F L288I L294P S295VY93Q S95D S111K D118K A136P D139R S202R R210G Q243K 10.8 A & H 44 C. 40hr 38.8 1165.6 W260F L288I L294P S295V Y93Q S95D D118K A136P D139R R185GS202R R210G W260F 10.8 A & H 44 C. 40 hr 39.9 1420.7 A276E L288I L294PS295V Y93Q S95D D118K A136P D139R S202R Q203T R210G W260F 10.8 A & H 44C. 40 hr 24.9 1530.3 A276E L288I L294P S295V Y93Q S95D D118K A136P D139RS202R R210G Q243K W260F 10.8 A & H 44 C. 40 hr 41.4 1313.7 N273D L288IL294P S295V Y93Q S95D D118K A136P D139R S202R R210G E234F Q243K 10.8 A &H 44 C. 40 hr 41.3 1607.1 W260F L288I L294P S295V N71S Y93Q S95D D118KA136P D139R S202R R210G Q243K 10.8 A & H 44 C. 40 hr 40.9 1693.9 W260FL288I L294P S295V Y93Q S95D N100H D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 40 hr 34.8 1271.7 A276E L288I L294P S295V E77K Y93QS95D D118K A136P D139R S202R R210G Q243K 10.8 A & H 44 C. 40 hr 21.61710.6 W260F L288I L294P S295V Y93Q S95D D118K A136P D139R S202R R210GW260F S266A 10.8 A & H 44 C. 40 hr 24.1 1908.7 A276E L288I L294P S295VN45G Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40hr 36.0 1986.4 A276E L288I L294P S295V Y93Q S95D S111A D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 40 hr 35.0 929.1 A276E L288I L294PS295V Y93Q S95D S98D D118K A136P D139R S202R R210G W260F 10.8 A & H 44C. 40 hr 22.7 435.3 A276E L288I L294P S295V A1V Y93Q S95D D118K A136PD139R S202R R210G Q243K 10.8 A & H 44 C. 40 hr 36.5 432.0 W260F L288IL294P S295V Y93Q S95D D118K A136P D139R S202R R210G Q243K W260F 10.8 A &H 44 C. 40 hr 34.7 431.2 N272T L288I L294P S295V T37P Y93Q S95D D118KA136P D139R S202R R210G Q243K 10.8 A & H 44 C. 40 hr 41.6 1025.9 W260FL288I L294P S295V N71S Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 40 hr 30.9 427.7 A276E L288I L294P S295V T37P Y93Q S95DD118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 47.8 1091.1A276E L288I L294P S295V G47A Y93Q S95D D118K A136P D139R S202R R210GW260F 10.8 A & H 44 C. 40 hr 22.1 1228.7 A276E L288I L294P S295V T37RY93Q S95D D118K A136P D139R S202R R210G Q243K 10.8 A & H 44 C. 40 hr34.5 1144.7 W260F L288I L294P S295V E77T Y93Q S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 40 hr 31.9 842.1 A276E L288I L294PS295V Y93Q S95D S111R D118K A136P D139R S202R R210G W260F 10.8 A & H 44C. 40 hr 32.1 717.2 A276E L288I L294P S295V Y93Q S95D D118K A136P D139RQ184K S202R R210G W260F 10.8 A & H 44 C. 40 hr 34.7 543.2 A276E L288IL294P S295V Y93Q S95D I114W D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 40 hr 20.8 836.3 A276E L288I L294P S295V Y93Q S95D D118K A136PD139R S202R R210G Q243K W260F 10.8 A & H 44 C. 40 hr 32.9 932.7 N273EL288I L294P S295V Y93Q S95D D118K A136P D139R N150S S202R R210G Q243K10.8 A & H 44 C. 40 hr 35.4 1186.9 W260F L288I L294P S295V Y93Q S95DD118K A136P D139R S202R R210G G257A W260F 10.8 A & H 44 C. 40 hr 30.3723.2 A276E L288I L294P S295V R70K Y93Q S95D D118K A136P D139R S202RR210G Q243K 10.8 A & H 44 C. 40 hr 32.1 955.5 W260F L288I L294P S295VY93Q S95D S111R D118K A136P D139R S202R R210G Q243K 10.8 A & H 44 C. 40hr 31.8 578.9 W260F L288I L294P S295V Y93Q S95D D118K A136P D139R S202RR210G Q243K W260F 10.8 A & H 44 C. 40 hr 31.7 933.9 N283W L288I L294PS295V Y93Q S95D D118K A136P D139R Q169K S202R R210G Q243K 10.8 A & H 44C. 40 hr 36.1 1395.8 W260F L288I L294P S295V Y93Q S95D D118K A136P D139RQ184K S202R R210G Q243K 10.8 A & H 44 C. 40 hr 29.6 983.4 W260F L288IL294P S295V Y93Q S95D S98P D118K A136P D139R S202R R210G Q243K 10.8 A &H 44 C. 40 hr 25.9 1183.3 W260F L288I L294P S295V Y93Q S95D D104G D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 34.8 1081.8 A276EL288I L294P S295V Y93Q S95D D118K A136P D139R S202R R210G Q243K W260F10.8 A & H 44 C. 40 hr 30.8 929.3 A276W L288I L294P S295V Y93Q S95DD118K A136P D139R Q184E S202R R210G Q243K 10.8 A & H 44 C. 40 hr 29.91051.1 W260F L288I L294P S295V D65E Y93Q S95D D118K A136P D139R S202RR210G W260F 10.8 A & H 44 C. 40 hr 27.0 1252.3 A276E L288I L294P S295VY93Q S95D D118K A136P D139R Y174L S202R R210G W260F 10.8 A & H 44 C. 40hr 28.0 1956.5 A276E L288I L294P S295V Y93Q S95D A97S D118K A136P D139RS202R R210G Q243K 10.8 A & H 44 C. 40 hr 22.9 1557.5 W260F L288I L294PS295V V82I Y93Q S95D D118K A136P D139R S202R R210G Q243K 10.8 A & H 44C. 40 hr 28.2 356.9 W260F L288I L294P S295V N18V Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 48.9 622.1 A276E L288IL294P S295V N18R Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 40 hr 27.1 354.0 A276E L288I L294P S295V Y93Q S95D S98D D118KA136P D139R S202R R210G Q243K 10.8 A & H 44 C. 40 hr 21.9 350.8 W260FL288I L294P S295V Y93Q S95D D118K A136P D139R K142M S202R R210G Q243K10.8 A & H 44 C. 40 hr 20.8 341.0 W260F L288I L294P S295V Y93Q S95DD118K A136P D139R R185G S202R R210G Q243K 10.8 A & H 44 C. 40 hr 26.6340.9 W260F L288I L294P S295V Y93Q S95D D118K A136P D139R Q169R S202RR210G Q243K 10.8 A & H 44 C. 40 hr 26.0 337.2 W260F L288I L294P S295VY93Q S95D D118K A136P D139R S202R R210G Q243K W260F 10.8 A & H 44 C. 40hr 25.8 336.3 S266A L288I L294P S295V Y93Q S95D D118K A136P D139R Q169AS202R R210G W260F 10.8 A & H 44 C. 40 hr 37.5 494.8 A276E L288I L294PS295V Y93Q S95D D118K A136P D139R N200T S202R R210G Q243K 10.8 A & H 44C. 40 hr 25.8 334.1 W260F L288I L294P S295V Y6M Y93Q S95D D118K A136PD139R S202R R210G Q243K 10.8 A & H 44 C. 40 hr 26.9 332.2 W260F L288IL294P S295V Y93Q S95D D118K A136P D139R E177S S202R R210G W260F 10.8 A &H 44 C. 40 hr 40.5 492.0 A276E L288I L294P S295V Y93Q S95D D118K A136PD139R E177Y S202R R210G W260F 10.8 A & H 44 C. 40 hr 46.5 589.4 A276EL288I L294P S295V Y93Q S95D D118K A136P D139R Q184S S202R R210G Q243K10.8 A & H 44 C. 40 hr 25.5 330.5 W260F L288I L294P S295V Y93Q S95DD118K A136P D139R Q184E S202R R210G W260F 10.8 A & H 44 C. 40 hr 41.5587.3 A276E L288I L294P S295V Y93Q S95D S111A D118K A136P D139R S202RR210G Q243K 10.8 A & H 44 C. 40 hr 25.3 329.0 W260F L288I L294P S295VY93Q S95D D118K A136P D139R Q184S S202R R210G W260F 10.8 A & H 44 C. 40hr 35.7 460.2 A276E L288I L294P S295V Y93Q S95D D118K A136P D139R S202RR210G T228S W260F 10.8 A & H 44 C. 40 hr 21.9 326.3 A276E L288I L294PS295V Y93Q S95D D118K A136P D139R S202R R210G E234F W260F 10.8 A & H 44C. 40 hr 41.9 518.2 A276E L288I L294P S295V Y93Q S95D D118K A136P D139RS202R R210G A235R Q243K 10.8 A & H 44 C. 40 hr 25.0 325.9 W260F L288IL294P S295V Y93Q S95D E108S D118K A136P D139R S202R R210G W260F 10.8 A &H 44 C. 40 hr 21.7 321.7 A276E L288I L294P S295V Y93Q S95D K116R D118KA136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 36.1 424.6 A276EL288I L294P S295V Y93Q S95D D118K T119R A136P D139R S202R R210G W260F10.8 A & H 44 C. 40 hr 22.6 304.8 A276E L288I L294P S295V Y93Q S95DD118K A136P D139R N200T S202R R210G W260F 10.8 A & H 44 C. 40 hr 44.9550.6 A276E L288I L294P S295V Y93Q S95D D118K A136P D139R N180R S202RR210G Q243K 10.8 A & H 44 C. 40 hr 29.4 320.9 W260F L288I L294P S295VY93Q S95D D118K A136P D139R P183G S202R R210G W260F 10.8 A & H 44 C. 40hr 37.8 426.7 A276E L288I L294P S295V Y93Q S95D D118K A136P D139R P183TS202R R210G W260F 10.8 A & H 44 C. 40 hr 37.1 421.8 A276E L288I L294PS295V Y93Q S95D D118K A136P D139R S202R R205K R210G Q243K 10.8 A & H 44C. 40 hr 27.0 319.7 W260F L288I L294P S295V Q35L Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 23.0 319.1 A276E L288IL294P S295V Y93Q S95D D118K A136P D139R S202R R210G W260F A276E 10.8 A &H 44 C. 40 hr 40.5 440.8 N279D L288I L294P S295V N18R Y93Q S95D D118KA136P D139R S202R R210G Q243K 10.8 A & H 44 C. 40 hr 24.3 318.7 W260FL288I L294P S295V G47S Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 44 C. 40 hr 24.5 316.5 A276E L288I L294P S295V D57N Y93Q S95DD118K A136P D139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 25.7 342.9A276E L288I L294P S295V E77K Y93Q S95D D118K A136P D139R S202R R210GW260F 10.8 A & H 44 C. 40 hr 26.5 532.8 A276E L288I L294P S295V Y93QS95D D118K A136P D139R S202R R210G A235K Q243K 10.8 A & H 44 C. 40 hr23.8 315.7 W260F L288I L294P S295V Y6H Y93Q S95D D118K A136P D139R S202RR210G Q243K 10.8 A & H 44 C. 40 hr 23.8 314.8 W260F L288I L294P S295VN45G Y93Q S95D D118K A136P D139R S202R R210G Q243K 10.8 A & H 44 C. 40hr 23.8 314.1 W260F L288I L294P S295V G47S Y93Q S95D D118K A136P D139RS202R R210G Q243K 10.8 A & H 44 C. 40 hr 24.4 297.8 W260F L288I L294PS295V Y93Q S95D K116R D118K A136P D139R S202R R210G Q243K 10.8 A & H 44C. 40 hr 21.3 291.6 W260F L288I L294P S295V D57N Y93Q S95D D118K A136PD139R S202R R210G Q243K 10.8 A & H 44 C. 40 hr 20.6 285.5 W260F L288IL294P S295V Y93Q S95D D118K A136P D139R S202R R210G Q243K W260F 10.8 A &H 44 C. 40 hr 20.4 284.0 N272M L288I L294P S295V Y93Q S95D D118K A136PD139R H172R S202R R210G Q243K 10.8 A & H 44 C. 40 hr 20.3 283.3 W260FL288I L294P S295V G47A Y93Q S95D D118K A136P D139R S202R R210G Q243K10.8 A & H 44 C. 40 hr 20.1 281.0 W260F L288I L294P S295V Y93Q S95DI114Q D118K A136P D139R S202R R210G Q243K 10.8 A & H 44 C. 40 hr 50.1357.4 W260F L288I L294P S295V Y93Q S95D D104G D118K A136P D139R S202RR210G Q243K 10.8 A & H 44 C. 40 hr 21.4 251.9 W260F L288I L294P S295VY93Q S95D D118K A136P D139R S202R R210G K254Y W260F 10.8 A & H 44 C. 40hr 29.4 275.5 A276E L288I L294P S295V Y93Q S95D S98T D118K A136P D139RS202R R210G W260F 10.8 A & H 44 C. 40 hr 26.2 372.4 A276E L288I L294PS295V Y93Q S95D D118K A136P D139R S202R R210G N213D W260F 10.8 A & H 44C. 40 hr 49.2 529.3 A276E L288I L294P S295V Y93Q S95D D118K E133R A136PD139R S202R R210G W260F 10.8 A & H 44 C. 40 hr 26.7 370.9 A276E L288IL294P S295V Y93Q S95D D118K A136P D139R K142S S202R R210G W260F 10.8 A &H 44 C. 40 hr 27.6 289.4 A276E L288I L294P S295V Y93Q S95D D118K A136PD139R K142V S202R R210G W260F 10.8 A & H 44 C. 40 hr 42.1 421.7 A276EL288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R P183G S202R 10.8A & H 44 C. 65 hr 47.3 2795.3 R210G W260F L288I L294P S295V A30T Q60RY93Q S95D I114Q D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr49.2 2933.3 W260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136PD139R Q143R S202R 10.8 A & H 44 C. 65 hr 42.0 2748.0 R210G W260F L288IL294P S295V A1V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A& H 44 C. 65 hr 45.7 2697.6 W260F L288I L294P S295V A30T Q60R K63Q Y93QS95D D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 26.6 1637.9W260F L288I L294P S295V A30T T37P Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 44 C. 65 hr 47.1 2909.1 W260F L288I L294P S295V S8TA30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr53.1 3150.8 W260F L288I L294P S295V A30T G47S Q60R Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 44 C. 65 hr 38.6 2182.8 W260F L288I L294PS295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 44 C.65 hr 36.9 2145.4 G257A W260F L288I L294P S295V A30T Q60R E77N Y93Q S95DD118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 42.7 2545.4 W260FL288I L294P S295V A30T Q60R Y93Q S95D D104A D118K A136P D139R S202R 10.8A & H 44 C. 65 hr 39.0 2295.9 R210G W260F L288I L294P S295V A30T Q60RY93Q S95D S111A D118K A136P D139R S202R 10.8 A & H 44 C. 65 hr 39.12359.6 R210G W260F L288I L294P S295V A30T Q60R Y93Q S95D S111R D118KA136P D139R S202R 10.8 A & H 44 C. 65 hr 39.0 2282.4 R210G W260F L288IL294P S295V A30T N45G Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8A & H 44 C. 65 hr 45.2 2715.3 W260F L288I L294P S295V N18V A30T Q60RY93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 46.12807.8 W260F L288I L294P S295V N18R A30T Q60R Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 44 C. 65 hr 38.8 2293.7 W260F L288I L294PS295V A30T Q60R N71S Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H44 C. 65 hr 42.3 2463.6 W260F L288I L294P S295V A30T Q60R S74K Y93Q S95DD118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 44.8 2612.3 W260FL288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R Y174L S202RR210G 10.8 A & H 44 C. 65 hr 45.2 2795.8 W260F L288I L294P S295V A30TQ60R Y93Q S95D D118K A136P D139R N180R S202R 10.8 A & H 44 C. 65 hr 49.33079.7 R210G W260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136PD139R Q169K S202R 10.8 A & H 44 C. 65 hr 42.8 2554.2 R210G W260F L288IL294P S295V A30T Q60R Y93Q S95D D118K A136P D139R E177S S202R 10.8 A & H44 C. 65 hr 46.5 2609.2 R210G W260F L288I L294P S295V A30T Q60R Y93QS95D D118K A136P D139R Q184K S202R 10.8 A & H 44 C. 65 hr 43.1 2535.5R210G W260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139RR185G S202R 10.8 A & H 44 C. 65 hr 48.6 2857.7 R210G W260F L288I L294PS295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 44 C.65 hr 39.8 2357.7 E234Y W260F L288I L294P S295V A30T Q60R Y93Q S95DD118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 37.1 2135.0 A235RW260F L288I L294P S295V A30T Q60R Y93Q S95D K116R D118K A136P D139RS202R 10.8 A & H 44 C. 65 hr 50.8 3230.0 R210G W260F L288I L294P S295VA30T Q60R Y93Q S95D D118K T119R A136P D139R S202R 10.8 A & H 44 C. 65 hr31.3 2027.8 R210G W260F L288I L294P S295V A30T Q60R Y93Q S95D D118KA136P D139R N200T S202R 10.8 A & H 44 C. 65 hr 48.9 3039.0 R210G W260FL288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R205K 10.8A & H 44 C. 65 hr 45.5 2711.0 R210G W260F L288I L294P S295V A30T Q60RY93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 46.52814.1 W260F N273E L288I L294P S295V Y6H A30T Q60R Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 44 C. 65 hr 47.2 2848.1 W260F L288I L294PS295V Y6M A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H44 C. 65 hr 47.1 2798.1 W260F L288I L294P S295V T11K A30T Q60R Y93Q S95DD118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 37.8 2188.6 W260FL288I L294P S295V A30T Q60R Y93Q S95D E108S D118K A136P D139R S202R 10.8A & H 44 C. 65 hr 39.0 2182.0 R210G W260F L288I L294P S295V A30T Q60RY93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 32.51854.4 K254Y W260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 44 C. 65 hr 39.9 2369.3 W260F S266A L288IL294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H44 C. 65 hr 25.9 1681.4 W260F A270N L288I L294P S295V A30T Q60R Y93QS95D D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 24.7 1394.7W260F L288I L294P S295G A30T Q60R Y93Q S95D A97R D118K A136P D139R S202RR210G 10.8 A & H 44 C. 65 hr 39.1 2310.5 W260F L288I L294P S295V A30TQ60R Y93Q S95D A97S D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr40.1 2255.1 W260F L288I L294P S295V A30T Q60R Y93Q S95D S98P D118K A136PD139R S202R R210G 10.8 A & H 44 C. 65 hr 52.3 3335.3 W260F L288I L294PS295V A30T Q60R Y93Q S95D I114M D118K A136P D139R S202R R210G 10.8 A & H44 C. 65 hr 44.1 2532.9 W260F L288I L294P S295V A30T Q60R Y93Q S95DI114W D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 46.9 2651.3W260F L288I L294P S295V A30T Q60R Y93Q S95D S98D D118K A136P D139R S202RR210G 10.8 A & H 44 C. 65 hr 54.3 3517.2 W260F L288I L294P S295V A30TQ60R Y93Q S95D D118K A136P D139R N200D S202R 10.8 A & H 44 C. 65 hr 37.32087.7 R210G W260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136PD139R S202R Q203T 10.8 A & H 44 C. 65 hr 43.8 2657.3 R210G W260F L288IL294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H44 C. 65 hr 37.4 2218.5 W260F L288I E290A L294P S295V A30T Q60R Y93QS95D D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 41.7 2490.0W260F L288I L294P S295V T296S A30T Q60R Y93Q S95D D118K A136P D139RS202R R210G 10.8 A & H 44 C. 65 hr 49.2 3067.7 N213D W260F L288I L294PS295V A30T D34N Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H44 C. 65 hr 28.7 1761.0 W260F L288I L294P S295V A30T Q60R Y93Q S95DD118K A136P D139R K142S S202R 10.8 A & H 44 C. 65 hr 43.9 2588.9 R210GW260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R K142VS202R 10.8 A & H 44 C. 65 hr 47.6 2852.4 R210G W260F L288I L294P S295VA30T D57N Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 44 C.65 hr 35.6 2011.7 W260F L288I L294P S295V A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 48.2 2825.5 W260F L288IL294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H44 C. 65 hr 55.5 3502.1 W260F T280L L288I L294P S295V A30T Q60R Y93QS95D D118K A136P D139R Y196W S202R 10.8 A & H 44 C. 65 hr 31.5 1838.6R210G W260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139RS202R R210G 10.8 A & H 44 C. 65 hr 49.7 3163.0 Q243H W260F L288I L294PS295V A30T Q60R K63R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H44 C. 65 hr 46.5 2717.0 W260F L288I L294P S295V S3P A30T Q60R Y93Q S95DD118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 51.4 3013.0 W260FL288I L294P S295V A30T Q60R A83P Y93Q S95D D118K A136P D139R S202R R210G10.8 A & H 44 C. 65 hr 49.7 2658.0 W260F L288I L294P S295V A30T G47AQ60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 39.12187.5 W260F L288I L294P S295V A30T Q60R E77T Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 44 C. 65 hr 51.6 3136.9 W260F L288I L294PS295V A30T Q60R H80K Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H44 C. 65 hr 47.4 2961.7 W260F L288I L294P S295V A30T Q60R Y93Q S95DD118K S131T A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 47.1 2775.9W260F L288I L294P S295V A30T Q60R Y93F S95D D118K A136P D139R S202RR210G 10.8 A & H 44 C. 65 hr 21.5 1286.1 W260F L288I L294P S295V A30TQ60R A83S Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr50.3 3011.0 W260F L288I L294P S295V F5H A30T Q60R Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 44 C. 65 hr 20.3 1252.3 W260F L288I L294PS295V A30T E41V Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H44 C. 65 hr 45.3 2662.8 W260F L288I L294P S295V A30T Q60R Y93Q S95DD104G D118K A136P D139R S202R 10.8 A & H 44 C. 65 hr 41.3 2462.0 R210GW260F L288I L294P S295V A30T Q60R D65E Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 44 C. 65 hr 41.4 2349.2 W260F L288I L294P S295V A30TQ60R R70K Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr51.0 2992.6 W260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136PD139R Q169A S202R 10.8 A & H 44 C. 65 hr 52.9 3075.6 R210G W260F L288IL294P S295V A30T Q60R Y93Q S95D D118K A136P D139R E177Y S202R 10.8 A & H44 C. 65 hr 55.7 3891.6 R210G W260F L288I L294P S295V A30T Q60R Y93QS95D D118K A136P D139R Q184E S202R 10.8 A & H 44 C. 65 hr 49.8 3312.0R210G W260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139RQ184S S202R 10.8 A & H 44 C. 65 hr 50.8 3160.9 R210G W260F L288I L294PS295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 44 C.65 hr 48.9 2634.7 R244K W260F L288I L294P S295V A30T Q60R Y93Q S95DD118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 56.0 3092.3 W260FN279D L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 44 C. 65 hr 66.6 5117.4 W260F N279E L288I L294P S295VA30T Q60R Y93Q S95D N100Y D118K A136P D139R S202R 10.8 A & H 44 C. 65 hr49.8 3141.8 R210G W260F L288I L294P S295V A30T Q60R Y93Q S95D N100HD118K A136P D139R S202R 10.8 A & H 44 C. 65 hr 50.3 3157.7 R210G W260FL288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8A & H 44 C. 65 hr 53.3 3241.2 W260F N273D L288I L294P S295V A30T Q60RY93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 47.02320.0 W260F N272M L288I L294P S295V A30T Q60R Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 44 C. 65 hr 49.4 2768.5 W260F N272T L288IL294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H44 C. 65 hr 54.3 3740.8 W260F N283W L288I L294P S295V A30T Q60R Y93QS95D D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 60.1 4037.2W260F A276D L288I L294P S295V T11R A30T Q60R Y93Q S95D D118K A136P D139RS202R R210G 10.8 A & H 44 C. 65 hr 44.0 2371.8 W260F L288I L294P S295VA30T Q60R Y93Q S95D D118K A136P D139R H172R S202R 10.8 A & H 44 C. 65 hr39.2 2255.2 R210G W260F L288I L294P S295V A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G T228S 10.8 A & H 44 C. 65 hr 32.1 1697.7 W260FL288I L294P S295V Y6F A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G10.8 A & H 44 C. 65 hr 53.6 3125.0 W260F L288I L294P S295V Y6W A30T Q60RY93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 53.93398.1 W260F L288I L294P S295V Y13F A30T Q60R Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 44 C. 65 hr 49.6 2960.8 W260F L288I L294PS295V Y13W A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H44 C. 65 hr 47.4 2383.8 W260F L288I L294P S295V A30T Q60R Y93Q S95DY105W D118K A136P D139R S202R 10.8 A & H 44 C. 65 hr 26.1 1360.3 R210GW260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R Y196FS202R R210G 10.8 A & H 44 C. 65 hr 42.7 2379.9 W260F L288I L294P S295VA30T Y32F Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 44 C.65 hr 52.2 2971.5 W260F L288I L294P S295V A30T Y32W Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 53.3 3465.5 W260F L288IL294P S295V A30T Q60R Y93W S95D D118K A136P D139R S202R R210G 10.8 A & H44 C. 65 hr 24.5 1463.7 W260F L288I L294P S295V A30T Q60R Y93Q S95DD118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 31.8 1852.5 W260FY262F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 44 C. 65 hr 26.7 1607.2 W260F Y286W L288I L294P S295VA30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 44 C. 65 hr29.1 1630.3 Q243K W260F L288I L294P S295V A30T G47K Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 44 C. 65 hr 38.1 2019.5 W260F L288IL294P S295V A30T Q60R Y93Q S95D D118K A136P D139R N150T S202R 10.8 A & H44 C. 65 hr 54.4 3989.6 R210G W260F L288I L294P S295V A30T Y93Q S95DD118K A136P D139R N180R N200T S202R 10.8 A & H 44 C. 90 hr 34.0 1648.9R210G W260F L288I L294P S295V A30T Y93Q S95D D118K A136P D139R Q184KN200T S202R 10.8 A & H 44 C. 90 hr 29.6 1503.4 R210G W260F L288I L294PS295V Y6M A30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H44 C. 90 hr 30.8 1487.3 W260F L288I L294P S295V A30T Y93Q S95D D118KA136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 32.0 1483.9 W260FT280L L288I L294P S295V A1V A30T Y93Q S95D D118K A136P D139R N200T S202RR210G 10.8 A & H 44 C. 90 hr 33.9 1534.7 W260F L288I L294P S295V A30TY93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr35.2 1649.1 Q243Y W260F L288I L294P S295V A30T Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 35.6 1592.4 Q243K W260FL288I L294P S295V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G10.8 A & H 44 C. 90 hr 37.6 1862.2 Q243H W260F L288I L294P S295V A30TK63R Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90hr 30.3 1518.5 W260F L288I L294P S295V S3P A30T Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 33.7 1687.5 W260F L288IL294P S295V A30T T37P Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8A & H 44 C. 90 hr 27.4 1334.2 W260F L288I L294P S295V A30T G47A Y93QS95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 21.91179.0 W260F L288I L294P S295V S8T A30T Y93Q S95D D118K A136P D139RN200T S202R R210G 10.8 A & H 44 C. 90 hr 30.3 1497.9 W260F L288I L294PS295V A30T G47S Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H44 C. 90 hr 29.4 1474.2 W260F L288I L294P S295V A30T H80K Y93Q S95DD118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 34.9 1724.2W260F L288I L294P S295V A30T V82I Y93Q S95D D118K A136P D139R N200TS202R R210G 10.8 A & H 44 C. 90 hr 26.5 1300.2 W260F L288I L294P S295VA30T A83S Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C.90 hr 36.0 1626.1 W260F L288I L294P S295V A30T G47K Y93Q S95D D118KA136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 32.1 1677.0 W260FL288I L294P S295V A30T H80R Y93Q S95D D118K A136P D139R N200T S202RR210G 10.8 A & H 44 C. 90 hr 38.1 1699.1 W260F L288I L294P S295V A30TY93Q S95D S111K D118K A136P D139R N200T S202R 10.8 A & H 44 C. 90 hr34.2 1626.1 R210G W260F L288I L294P S295V A30T D65E Y93Q S95D D118KA136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 24.9 1205.6 W260FL288I L294P S295V A30T T37R Y93Q S95D D118K A136P D139R N200T S202RR210G 10.8 A & H 44 C. 90 hr 42.5 2123.6 W260F L288I L294P S295V A30TR70K Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90hr 38.7 1961.5 W260F L288I L294P S295V A30T N45G Y93Q S95D D118K A136PD139R N200T S202R 10.8 A & H 44 C. 90 hr 28.9 1308.4 R210G W260F L288IL294P S295V N18V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8A & H 44 C. 90 hr 39.2 1811.9 W260F L288I L294P S295V N18R A30T Y93QS95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 36.31722.7 W260F L288I L294P S295V A30T N71S Y93Q S95D D118K A136P D139RN200T S202R R210G 10.8 A & H 44 C. 90 hr 29.7 1411.0 W260F L288I L294PS295V A30T S74K Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H44 C. 90 hr 32.8 1520.0 W260F L288I L294P S295V A30T Y93Q S95D D118KA136P D139R Y174R N200T S202R 10.8 A & H 44 C. 90 hr 27.9 1362.6 R210GW260F L288I L294P S295V A30T Y93Q S95D D118K A136P D139R Y174L N200TS202R 10.8 A & H 44 C. 90 hr 24.8 1250.7 R210G W260F L288I L294P S295VA30T Y93Q S95D D118K A136P D139R Q169R N200T S202R 10.8 A & H 44 C. 90hr 34.9 1585.4 R210G W260F L288I L294P S295V A30T Y93Q S95D D118K A136PD139R Q169K N200T S202R 10.8 A & H 44 C. 90 hr 29.0 1449.3 R210G W260FL288I L294P S295V A30T Y93Q S95D D118K A136P D139R E177S N200T S202R10.8 A & H 44 C. 90 hr 32.5 1560.9 R210G W260F L288I L294P S295V A30TY93Q S95D D118K A136P D139R N150S N200T S202R 10.8 A & H 44 C. 90 hr32.6 1574.2 R210G W260F L288I L294P S295V A30T Y93Q S95D D118K A136PD139R N150R N200T S202R 10.8 A & H 44 C. 90 hr 30.6 1427.1 R210G W260FL288I L294P S295V A30T Y93Q S95D D118K A136P D139R R185G N200T S202R10.8 A & H 44 C. 90 hr 37.4 2024.0 R210G W260F L288I L294P S295V A30TY93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr22.3 1152.3 E234F W260F L288I L294P S295V A30T Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 32.4 1743.7 E234Y W260FL288I L294P S295V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G10.8 A & H 44 C. 90 hr 33.5 1457.1 A235R W260F L288I L294P S295V A30TY93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr33.9 1412.3 A235K W260F L288I L294P S295V A30T Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 36.0 1587.9 R244K W260FL288I L294P S295V A30T Y93Q S95D K116R D118K A136P D139R N200T S202R10.8 A & H 44 C. 90 hr 41.4 1842.3 R210G W260F L288I L294P S295V A30TY93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr45.5 2149.3 W260F N279E L288I L294P S295V A30T Y93Q S95D N100Y D118KA136P D139R N200T S202R 10.8 A & H 44 C. 90 hr 33.0 1741.2 R210G W260FL288I L294P S295V A30T Y93Q S95D N100H D118K A136P D139R N200T S202R10.8 A & H 44 C. 90 hr 38.8 1838.0 R210G W260F L288I L294P S295V A30TY93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr39.0 1881.0 W260F N273D L288I L294P S295V A30T Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 36.5 1799.3 W260F N273EL288I L294P S295V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G10.8 A & H 44 C. 90 hr 32.8 1638.4 W260F N272T L288I L294P S295V A30TY93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr32.1 1506.8 W260F N283W L288I L294P S295V A30T Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 48.9 2550.1 W260F N283HL288I L294P S295V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G10.8 A & H 44 C. 90 hr 30.6 1421.9 W260F A276W L288I L294P S295V T11KA30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90hr 32.5 1434.9 W260F L288I L294P S295V T11R A30T Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 28.8 1357.2 W260F L288IL294P S295V A30T D57N Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8A & H 44 C. 90 hr 35.7 1691.4 W260F L288I L294P S295V A30T Y93Q S95DE108S D118K A136P D139R N200T S202R 10.8 A & H 44 C. 90 hr 29.1 1448.2R210G W260F L288I L294P S295V A30T Y93Q S95D D118K A136P D139R H172RN200T S202R 10.8 A & H 44 C. 90 hr 30.7 1425.1 R210G W260F L288I L294PS295V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44C. 90 hr 20.2 1075.2 T228S W260F L288I L294P S295V A30T Y93Q S95D D118KA136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 37.8 1680.7 W260FS266A L288I L294P S295V A30T Y93Q S95D D118K A136P D139R N200T S202RR210G 10.8 A & H 44 C. 90 hr 23.7 1147.5 W260F L288I L294K S295G A30TY93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr33.6 1575.8 W260F L288I L294P S295V Y6F A30T Y93Q S95D D118K A136P D139RN200T S202R R210G 10.8 A & H 44 C. 90 hr 27.3 1331.5 W260F L288I L294PS295V A1G A30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H44 C. 90 hr 37.9 1718.8 W260F L288I L294P S295V A30T E77T Y93Q S95DD118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 36.1 1832.4W260F L288I L294P S295V A30T Y93Q S95D D118K S131T A136P D139R N200TS202R 10.8 A & H 44 C. 90 hr 37.7 1520.1 R210G W260F L288I L294P S295VA30T G59Q Y93Q S95D D118K A136P D139R N200T S202R 10.8 A & H 44 C. 90 hr32.3 1258.3 R210G W260F L288I L294P S295V A30T Y32W Y93Q S95D D118KA136P D139R N200T S202R 10.8 A & H 44 C. 90 hr 45.5 1710.8 R210G W260FL288I L294P S295V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G10.8 A & H 44 C. 90 hr 54.1 2621.3 G257A W260F L288I L294P S295V A30TY93Q S95D D104G D118K A136P D139R N200T S202R 10.8 A & H 44 C. 90 hr30.7 1433.7 R210G W260F L288I L294P S295V A30T Q35L Y93Q S95D D118KA136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 29.8 1459.5 W260FL288I L294P S295V A30T Y93Q S95D D118K A136P D139R Q169A N200T S202R10.8 A & H 44 C. 90 hr 32.0 1473.3 R210G W260F L288I L294P S295V A30TY93Q S95D D118K A136P D139R Q184E N200T S202R 10.8 A & H 44 C. 90 hr39.1 1756.9 R210G W260F L288I L294P S295V A30T Y93Q S95D D118K A136PD139R Q184S N200T S202R 10.8 A & H 44 C. 90 hr 34.9 1619.3 R210G W260FL288I L294P S295V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G10.8 A & H 44 C. 90 hr 44.8 2089.3 W260F A276D L288I L294P S295V A30TY93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr22.3 1256.7 N229D W260F L288I L294P S295V A30T Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 24.0 1226.4 W260F A270DL288I L294P S295V A30T Y93Q S95D A97R D118K A136P D139R N200T S202RR210G 10.8 A & H 44 C. 90 hr 28.3 1441.4 W260F L288I L294P S295V A30TY93Q S95D A97S D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90hr 29.0 1362.3 W260F L288I L294P S295V A30T Y93Q S95D S98P D118K A136PD139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 34.4 1591.0 W260F L288IL294P S295V A30T Y93F S95D D118K A136P D139R N200T S202R R210G 10.8 A &H 44 C. 90 hr 27.2 1431.9 W260F L288I L294P S295V A30T Y93Q S95D I114MD118K A136P D139R N200T S202R 10.8 A & H 44 C. 90 hr 33.0 1543.4 R210GW260F L288I L294P S295V A30T Y93Q S95D S98D D118K A136P D139R N200TS202R R210G 10.8 A & H 44 C. 90 hr 41.4 1784.8 W260F L288I L294P S295VA30T Y93Q S95D I114W D118K A136P D139R N200T S202R 10.8 A & H 44 C. 90hr 43.5 1831.3 R210G W260F L288I L294P S295V A30T Y93Q S95D S98T D118KA136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 31.9 1389.5 W260FL288I L294P S295V A30T Y93Q S95D I114Q D118K A136P D139R N200T S202R10.8 A & H 44 C. 90 hr 37.3 1722.1 R210G W260F L288I L294P S295V A30TY93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr24.8 972.4 W260F L288I E290A L294P S295V A30T Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 32.7 1586.6 W260F L288IL294P S295V T296S A30T Y93Q S95D D118K A136P D139R N200T S202R R210G10.8 A & H 44 C. 90 hr 29.5 1534.0 W260F L288I L294P S295V F298Y A30TY93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr40.3 1870.9 N213V W260F L288I L294P S295V A30T Y93Q S95D D118K A136PD139R K142M N200T S202R 10.8 A & H 44 C. 90 hr 37.4 1637.0 R210G W260FL288I L294P S295V A30T Y93Q S95D D118K A136P D139R K142S N200T S202R10.8 A & H 44 C. 90 hr 25.5 1345.5 R210G W260F L288I L294P S295V A30TY93Q S95D D118K A136P D139R K142V N200T S202R 10.8 A & H 44 C. 90 hr25.9 1287.8 R210G W260F L288I L294P S295V Y6W A30T Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 37.9 1736.3 W260F L288IL294P S295V Y13F A30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8A & H 44 C. 90 hr 34.5 1581.6 W260F L288I L294P S295V A30T Y93Q S95DD118K A136P D139R Y174F N200T S202R 10.8 A & H 44 C. 90 hr 36.5 1665.3R210G W260F L288I L294P S295V A30T Y93Q S95D D118K A136P D139R Y174WN200T S202R 10.8 A & H 44 C. 90 hr 32.2 1490.2 R210G W260F L288I L294PS295V A30T Y32F Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H44 C. 90 hr 43.7 1695.0 W260F L288I L294P S295V A30T Y93Q S95D D118KA136P D139R N200T S202R R210G 10.8 A & H 44 C. 90 hr 36.1 1638.2 W260FY286F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R Q184KS202R 10.8 A & H 46 C. 65 hr 35.6 2881.6 R210G W260F N279E L288I L294PS295V A30T Q60R Y93Q S95D D118K A136P D139R N200T S202R 10.8 A & H 46 C.65 hr 42.2 3258.3 R210G W260F N279E L288I L294P S295V A30T Q60R Y93QS95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 36.8 2859.1W260F N272T N279E L288I L294P S295V A30T Q60R Y93Q S95D I114W D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 33.0 2763.9 W260F N279EL288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202R Q203T 10.8A & H 46 C. 65 hr 38.4 3073.3 R210G W260F N279E L288I L294P S295V A1VA30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr42.8 3390.6 W260F N279E L288I L294P S295V A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 43.7 3511.5 Q243Y W260FN279E L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 43.3 3542.4 Q243K W260F N279E L288I L294PS295V S3P A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H46 C. 65 hr 44.3 3584.8 W260F N279E L288I L294P S295V A30T T37P Q60RY93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 37.43031.7 W260F N279E L288I L294P S295V A30T G47A Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 28.9 2315.8 W260F N279EL288I L294P S295V S8T A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G10.8 A & H 46 C. 65 hr 40.6 3234.7 W260F N279E L288I L294P S295V A30TQ60R E77T Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr22.0 1640.0 W260F N279E L288I L294P S295V A30T G47S Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 30.4 2542.5 W260F N279EL288I L294P S295V A30T Q60R H80K Y93Q S95D D118K A136P D139R S202R R210G10.8 A & H 46 C. 65 hr 38.0 2954.9 W260F N279E L288I L294P S295V A30TQ60R Y93Q S95D D118K S131T A136P D139R S202R R210G 10.8 A & H 46 C. 65hr 40.7 3104.4 W260F N279E L288I L294P S295V A30T Q60R A83S Y93Q S95DD118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 48.0 3945.5 W260FN279E L288I L294P S295V A30T Q60R E77N Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 36.6 2891.0 W260F N279E L288I L294P S295VA30T G47K Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C.65 hr 32.7 2634.8 W260F N279E L288I L294P S295V A30T Q60R H80R Y93Q S95DD118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 36.1 2891.2 W260FN279E L288I L294P S295V A30T E41V Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 27.5 2038.5 W260F N279E L288I L294P S295VA30T Q60R Y93Q S95D S111K D118K A136P D139R S202R 10.8 A & H 46 C. 65 hr41.8 3337.2 R210G W260F N279E L288I L294P S295V A30T T37R Q60R Y93Q S95DD118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 52.2 3975.3 W260FN279E L288I L294P S295V A30T Q60R R70K Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 37.1 3124.8 W260F N279E L288I L294P S295VA30T N45G Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C.65 hr 39.0 2947.1 W260F N279E L288I L294P S295V N18V A30T Q60R Y93Q S95DD118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 43.4 3304.6 W260FN279E L288I L294P S295V N18R A30T Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 32.0 2642.5 W260F N279E L288I L294P S295VA30T Q60R N71S Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C.65 hr 45.8 3839.1 W260F N279E L288I L294P S295V A30T Q60R Y93Q S95DD118K A136P D139R N180R S202R 10.8 A & H 46 C. 65 hr 39.0 3111.0 R210GW260F N279E L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139RQ169R S202R 10.8 A & H 46 C. 65 hr 39.9 3254.8 R210G W260F N279E L288IL294P S295V A30T Q60R Y93Q S95D D118K A136P D139R E177S S202R 10.8 A & H46 C. 65 hr 35.2 2874.7 R210G W260F N279E L288I L294P S295V A30T Q60RY93Q S95D D118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 39.23337.4 R210G W260F N279E L288I L294P S295V A30T Q60R Y93Q S95D D118KA136P D139R N150S S202R 10.8 A & H 46 C. 65 hr 40.8 3202.1 R210G W260FN279E L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R N150RS202R 10.8 A & H 46 C. 65 hr 38.3 3091.3 R210G W260F N279E L288I L294PS295V A30T Q60R Y93Q S95D D118K A136P D139R Q184E S202R 10.8 A & H 46 C.65 hr 44.9 3681.2 R210G W260F N279E L288I L294P S295V A30T Q60R Y93QS95D D118K A136P D139R Q184S S202R 10.8 A & H 46 C. 65 hr 36.4 2548.9R210G W260F N279E L288I L294P S295V A30T Q60R Y93Q S95D D118K A136PD139R R185G S202R 10.8 A & H 46 C. 65 hr 38.7 3190.8 R210G W260F N279EL288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8A & H 46 C. 65 hr 29.9 2460.6 E234Y W260F N279E L288I L294P S295V A30TQ60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 31.32401.4 A235R W260F N279E L288I L294P S295V A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 35.5 2723.2 A235K W260FN279E L288I L294P S295V A30T Q60R Y93Q S95D K116R D118K A136P D139RS202R 10.8 A & H 46 C. 65 hr 45.1 3500.9 R210G W260F N279E L288I L294PS295V A30T Q60R Y93Q S95D D118K T119R A136P D139R S202R 10.8 A & H 46 C.65 hr 31.9 2771.9 R210G W260F N279E L288I L294P S295V A30T Q60R Y93QS95D N100H D118K A136P D139R S202R 10.8 A & H 46 C. 65 hr 35.3 2706.2R210G W260F N279E L288I L294P S295V A30T Q60R Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 46 C. 65 hr 37.4 3060.8 W260F N273D N279EL288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8A & H 46 C. 65 hr 39.2 3145.5 W260F N273E N279E L288I L294P S295V Y6HA30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr37.1 2783.9 W260F N279E L288I L294P S295V Y6M A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 39.2 3121.4 W260F N279EL288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8A & H 46 C. 65 hr 44.4 3317.0 W260F A276E N279E L288I L294P S295V T11KA30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr34.7 2624.4 W260F N279E L288I L294P S295V T11R A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 31.8 2663.3 W260F N279EL288I L294P S295V A30T Q60R Y93F S95D D118K A136P D139R S202R R210G 10.8A & H 46 C. 65 hr 35.2 2637.3 W260F N279E L288I L294P S295V A30T Q60RY93Q S95D I114M D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr41.7 3445.3 W260F N279E L288I L294P S295V A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 37.7 2883.4 W260F A276WN279E L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 39.1 3107.7 W260F A276D N279E L288I L294PS295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C.65 hr 36.9 3012.1 W260F N279E T280L L288I L294P S295V A30T Q60R Y93QS95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 32.7 2644.7W260F N279E N283W L288I L294P S295V A30T Q60R Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 46 C. 65 hr 38.8 3000.0 W260F N279E N283HL288I L294P S295V A30T Q60R Y93Q S95D S98D D118K A136P D139R S202R R210G10.8 A & H 46 C. 65 hr 46.0 3689.0 W260F N279E L288I L294P S295V A30TQ60R Y93Q S95D D118K A136P D139R N200D S202R 10.8 A & H 46 C. 65 hr 35.42809.9 R210G W260F N279E L288I L294P S295V A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 36.3 2755.5 W260F N279EL288I L294P S295V T296S A30T Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 38.8 3134.1 N213V W260F N279E L288I L294PS295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C.65 hr 35.7 2924.9 N213D W260F N279E L288I L294P S295V A30T Q60R Y93QS95D D118K A136P D139R K142M S202R 10.8 A & H 46 C. 65 hr 36.4 2818.9R210G W260F N279E L288I L294P S295V A30T Q60R Y93Q S95D D118K A136PD139R K142V S202R 10.8 A & H 46 C. 65 hr 42.7 3371.5 R210G W260F N279EL288I L294P S295V A30T D57N Q60R Y93Q S95D D118K A136P D139R S202R R210G10.8 A & H 46 C. 65 hr 36.8 2863.3 W260F N279E L288I L294P S295V Y6FA30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr32.7 2642.5 W260F N279E L288I L294P S295V Y6W A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 37.9 3066.9 W260F N279EL288I L294P S295V Y13W A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G10.8 A & H 46 C. 65 hr 32.7 2600.1 W260F N279E L288I L294P S295V A30TQ60R Y93Q S95D D118K A136P D139R Y174W S202R 10.8 A & H 46 C. 65 hr 33.32695.3 R210G W260F N279E L288I L294P S295V A30T Q60R Y93Q S95D D118KA136P D139R Y196F S202R R210G 10.8 A & H 46 C. 65 hr 28.6 2363.9 W260FN279E L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R N150TQ184E S202R 10.8 A & H 46 C. 65 hr 28.4 1889.2 R210G W260F L288I L294PS295V A30T Q60R Y93Q S95D D118K T119R A136P D139R N150T S202R 10.8 A & H46 C. 65 hr 22.0 1524.7 R210G W260F L288I L294P S295V Y6H A30T Q60R Y93QS95D D118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 27.4 2097.1R210G W260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139RN150T S202R 10.8 A & H 46 C. 65 hr 36.8 2701.3 R210G W260F T280L L288IL294P S295V A30T Q60R Y93Q S95D S98D D118K A136P D139R N150T S202R 10.8A & H 46 C. 65 hr 35.2 2427.4 R210G W260F L288I L294P S295V A1V A30TQ60R Y93Q S95D D118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 43.72601.1 R210G W260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136PD139R N150T S202R 10.8 A & H 46 C. 65 hr 43.2 3216.0 R210G Q243Y W260FL288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R N150T S202R 10.8A & H 46 C. 65 hr 43.5 3026.6 R210G Q243K W260F L288I L294P S295V A30TQ60R Y93Q S95D D118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 40.42777.9 R210G Q243H W260F L288I L294P S295V A30T T37P Q60R Y93Q S95DD118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 34.7 2415.7 R210GW260F L288I L294P S295V A30T G47A Q60R Y93Q S95D D118K A136P D139R N150TS202R 10.8 A & H 46 C. 65 hr 26.6 1790.0 R210G W260F L288I L294P S295VS8T A30T Q60R Y93Q S95D D118K A136P D139R N150T S202R 10.8 A & H 46 C.65 hr 34.4 2322.7 R210G W260F L288I L294P S295V A30T Q60R H80K Y93Q S95DD118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 42.3 2891.5 R210GW260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R N150TS202R 10.8 A & H 46 C. 65 hr 43.6 3149.9 R210G W260F A276E L288I L294PS295V A30T Q60R H80R Y93Q S95D D118K A136P D139R N150T S202R 10.8 A & H46 C. 65 hr 31.0 2937.8 R210G W260F L288I L294P S295V A30T Q60R Y93QS95D S111R D118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 27.32290.8 R210G W260F L288I L294P S295V A30T Q60R D65E Y93Q S95D D118KA136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 32.3 2405.0 R210G W260FL288I L294P S295V A30T T37R Q60R Y93Q S95D D118K A136P D139R N150T S202R10.8 A & H 46 C. 65 hr 38.4 2683.3 R210G W260F L288I L294P S295V A30TQ60R R70K Y93Q S95D D118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr33.0 2130.6 R210G W260F L288I L294P S295V A30T N45G Q60R Y93Q S95D D118KA136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 36.8 2514.4 R210G W260FL288I L294P S295V N18R A30T Q60R Y93Q S95D D118K A136P D139R N150T S202R10.8 A & H 46 C. 65 hr 33.2 2164.0 R210G W260F L288I L294P S295V A30TQ60R N71S Y93Q S95D D118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr36.0 2440.3 R210G W260F L288I L294P S295V A30T Q60R Y93Q S95D D118KA136P D139R N150T N180R S202R 10.8 A & H 46 C. 65 hr 36.3 2430.5 R210GW260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R N150TQ169R 10.8 A & H 46 C. 65 hr 32.4 2305.0 S202R R210G W260F L288I L294PS295V A30T Q60R Y93Q S95D D118K A136P D139R N150T E177S S202R 10.8 A & H46 C. 65 hr 39.8 2695.4 R210G W260F L288I L294P S295V A30T Q60R Y93QS95D D118K A136P D139R N150S S202R 10.8 A & H 46 C. 65 hr 36.7 2444.4R210G W260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139RN150R S202R 10.8 A & H 46 C. 65 hr 41.1 2760.3 R210G W260F L288I L294PS295V A30T Q60R Y93Q S95D D118K A136P D139R N150T Q184K S202R 10.8 A & H46 C. 65 hr 35.7 2509.9 R210G W260F L288I L294P S295V A30T Q60R Y93QS95D D118K A136P D139R N150T Q184S S202R 10.8 A & H 46 C. 65 hr 23.81711.4 R210G W260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136PD139R N150T R185G 10.8 A & H 46 C. 65 hr 35.1 2340.5 S202R R210G W260FL288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R N150T S202R 10.8A & H 46 C. 65 hr 29.0 1825.1 R210G A235R W260F L288I L294P S295V A30TQ60R Y93Q S95D D118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 34.82426.7 R210G A235K W260F L288I L294P S295V A30T Q60R Y93Q S95D D118KA136P D139R N150T N200T S202R 10.8 A & H 46 C. 65 hr 39.5 2836.9 R210GW260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R N150TS202R 10.8 A & H 46 C. 65 hr 46.1 2769.7 R210G W260F N279D L288I L294PS295V A30T Q60R Y93Q S95D N100H D118K A136P D139R N150T S202R 10.8 A & H46 C. 65 hr 23.6 1711.4 R210G W260F L288I L294P S295V A30T Q60R Y93QS95D D118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 51.7 3157.8R210G W260F N273D L288I L294P S295V A30T Q60R Y93Q S95D D118K A136PD139R N150T S202R 10.8 A & H 46 C. 65 hr 27.7 2016.5 R210G W260F N273EL288I L294P S295V Y6M A30T Q60R Y93Q S95D D118K A136P D139R N150T S202R10.8 A & H 46 C. 65 hr 31.1 2149.0 R210G W260F L288I L294P S295V A30TQ60R Y93Q S95D D118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 34.72194.5 R210G W260F N272M L288I L294P S295V A30T Q60R Y93Q S95D D118KA136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 39.9 2527.9 R210G W260FN272T L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R N150TS202R 10.8 A & H 46 C. 65 hr 38.5 2288.2 R210G W260F N283W L288I L294PS295V A30T Q60R Y93Q S95D D118K A136P D139R N150T S202R 10.8 A & H 46 C.65 hr 43.4 2810.4 R210G W260F N283H L288I L294P S295V A30T Q60R Y93QS95D D118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 45.9 2725.6R210G W260F A276W L288I L294P S295V A30T Q60R Y93Q S95D D118K A136PD139R N150T S202R 10.8 A & H 46 C. 65 hr 29.4 2120.6 R210G W260F A276DL288I L294P S295V T11K A30T Q60R Y93Q S95D D118K A136P D139R N150T S202R10.8 A & H 46 C. 65 hr 28.0 2038.5 R210G W260F L288I L294P S295V T11RA30T Q60R Y93Q S95D D118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr29.2 2046.6 R210G W260F L288I L294P S295V A30T Q60R Y93Q S95D D118KA136P D139R N150T S202R Q203T 10.8 A & H 46 C. 65 hr 37.6 2271.6 R210GW260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R N150TS202R 10.8 A & H 46 C. 65 hr 28.8 2052.5 R210G W260F L288I L294P S295VT296S A30T Q60R Y93Q S95D D118K A136P D139R N150T S202R 10.8 A & H 46 C.65 hr 36.1 2465.8 R210G W260F L288I L294P S295V F298Y A30T Q60R Y93QS95D D118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 42.3 2753.1R210G N213D W260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136PD139R K142M N150T 10.8 A & H 46 C. 65 hr 41.2 2823.7 S202R R210G W260FL288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R K142V N150TS202R 10.8 A & H 46 C. 65 hr 35.0 2438.7 R210G W260F L288I L294P S295VA30T D57N Q60R Y93Q S95D D118K A136P D139R N150T S202R 10.8 A & H 46 C.65 hr 35.7 2173.7 R210G W260F L288I L294P S295V Y6F A30T Q60R Y93Q S95DD118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 30.7 1988.5 R210GW260F L288I L294P S295V Y6W A30T Q60R Y93Q S95D D118K A136P D139R N150TS202R 10.8 A & H 46 C. 65 hr 33.4 2310.0 R210G W260F L288I L294P S295VY13F A30T Q60R Y93Q S95D D118K A136P D139R N150T S202R 10.8 A & H 46 C.65 hr 39.1 2559.7 R210G W260F L288I L294P S295V A30T Q60R Y93Q S95DD118K A136P D139R N150T Y174W 10.8 A & H 46 C. 65 hr 21.8 1712.3 S202RR210G W260F L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139RN150T Y196F S202R 10.8 A & H 46 C. 65 hr 24.8 1719.0 R210G W260F L288IL294P S295V A30T Q60R Y93Q S95D D118K A136P D139R N150T Y196W 10.8 A & H46 C. 65 hr 22.4 1640.5 S202R R210G W260F L288I L294P S295V A30T Y32WQ60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 43.53997.8 W260F N279E L288I L294P S295V A30T Q60R Y93W S95D D118K A136PD139R S202R R210G 10.8 A & H 46 C. 65 hr 20.3 2132.1 W260F N279E L288IL294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H46 C. 65 hr 20.3 2082.8 W260F Y262F N279E L288I L294P S295V A30T Q60RY93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 31.93054.0 W260F N279E Y286F L288I L294P S295V A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 22.6 2438.9 W260F N279EY286W L288I L294P S295V A30T Q60R Y93Q S95D A136P D139R S202R R210GW260F 10.8 A & H 46 C. 65 hr 34.1 3243.7 N279E L288I L294P S295V A30TQ60R Y93Q S95D D118K A136P D139R R210G W260F 10.8 A & H 46 C. 65 hr 32.72976.0 N279E L288I L294P S295V A30T Y32F Q60R Y93Q S95D D118K A136PD139R N150T S202R 10.8 A & H 46 C. 65 hr 22.6 1640.5 R210G W260F L288IL294P S295V A30T Y32W Q60R Y93Q S95D D118K A136P D139R N150T S202R 10.8A & H 46 C. 65 hr 26.6 2280.7 R210G W260F L288I L294P S295V A30T Q60RY93Q S95D D118K A136P D139R N150T S202R 10.8 A & H 46 C. 65 hr 21.01949.9 R210G W260F Y286F L288I L294P S295V A30T Y32F Y93Q S95D D118KA136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 36.2 2897.8 W260FN283H L288I L294P S295V A30T Y32W Y93Q S95D D118K A136P D139R N200TS202R 10.8 A & H 46 C. 65 hr 20.8 2361.1 R210G W260F N283H L288I L294PS295V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46C. 65 hr 20.2 1973.7 W260F N283H Y286F L288I L294P S295V A30T Y93Q S95DD118K A136P D139R E177Y N200T S202R 10.8 A & H 46 C. 65 hr 31.7 2229.3R210G W260F N283H L288I L294P S295V A30T Y93Q S95D D118K A136P D139RN200T S202R R210G 10.8 A & H 46 C. 65 hr 24.3 1923.2 A235R W260F N283HL288I L294P S295V Y6M A30T Y93Q S95D D118K A136P D139R N200T S202R R210G10.8 A & H 46 C. 65 hr 28.4 1979.1 W260F N283H L288I L294P S295V A30TD57N Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65hr 28.0 2061.9 W260F N283H L288I L294P S295V A30T Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 32.5 2191.2 W260F N279DN283H L288I L294P S295V A1G A30T Y93Q S95D D118K A136P D139R N200T S202RR210G 10.8 A & H 46 C. 65 hr 34.5 2510.0 W260F N283H L288I L294P S295VA1V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C.65 hr 35.3 2341.9 W260F N283H L288I L294P S295V A30T Y93Q S95D D118KA136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 39.0 2677.5 Q243YW260F N283H L288I L294P S295V A30T Y93Q S95D D118K A136P D139R N200TS202R R210G 10.8 A & H 46 C. 65 hr 40.9 2686.4 Q243K W260F N283H L288IL294P S295V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A &H 46 C. 65 hr 33.7 2380.1 Q243H W260F N283H L288I L294P S295V A30T K63RY93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr26.8 2057.0 W260F N283H L288I L294P S295V A30T T37P Y93Q S95D D118KA136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 30.3 2085.2 W260FN283H L288I L294P S295V A30T G47A Y93Q S95D D118K A136P D139R N200TS202R R210G 10.8 A & H 46 C. 65 hr 24.6 1875.9 W260F N283H L288I L294PS295V S8T A30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H46 C. 65 hr 35.8 2485.6 W260F N283H L288I L294P S295V A30T G47S Y93QS95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 33.82601.8 W260F N283H L288I L294P S295V A30T H80K Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 31.4 2232.0 W260F N283HL288I L294P S295V A30T Y93Q S95D D118K S131T A136P D139R N200T S202R10.8 A & H 46 C. 65 hr 28.6 1997.2 R210G W260F N283H L288I L294P S295VA30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65hr 37.5 2607.4 W260F A276E N283H L288I L294P S295V A30T E77N Y93Q S95DD118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 31.7 2443.3W260F N283H L288I L294P S295V A30T G47K Y93Q S95D D118K A136P D139RN200T S202R R210G 10.8 A & H 46 C. 65 hr 31.6 2377.1 W260F N283H L288IL294P S295V A30T H80R Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8A & H 46 C. 65 hr 25.4 1742.6 W260F N283H L288I L294P S295V A30T E41VY93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr37.3 2653.0 W260F N283H L288I L294P S295V A30T Y93Q S95D S111K D118KA136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 33.4 2327.5 R210G W260FN283H L288I L294P S295V A30T D65E Y93Q S95D D118K A136P D139R N200TS202R R210G 10.8 A & H 46 C. 65 hr 27.3 1902.6 W260F N283H L288I L294PS295V A30T T37R Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H46 C. 65 hr 33.5 2236.0 W260F N283H L288I L294P S295V A30T R70K Y93QS95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 33.22364.3 W260F N283H L288I L294P S295V A30T N45G Y93Q S95D D118K A136PD139R N200T S202R 10.8 A & H 46 C. 65 hr 34.8 2478.3 R210G W260F N283HL288I L294P S295V A30T Q35L Y93Q S95D D118K A136P D139R N200T S202RR210G 10.8 A & H 46 C. 65 hr 26.5 1994.9 W260F N283H L288I L294P S295VN18V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C.65 hr 38.8 2723.0 W260F N283H L288I L294P S295V N18R A30T Y93Q S95DD118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 23.5 1820.4W260F N283H L288I L294P S295V A30T N71S Y93Q S95D D118K A136P D139RN200T S202R R210G 10.8 A & H 46 C. 65 hr 30.6 2090.8 W260F N283H L288IL294P S295V A30T Y93Q S95D D118K A136P D139R N180R N200T S202R 10.8 A &H 46 C. 65 hr 31.1 2339.1 R210G W260F N283H L288I L294P S295V A30T Y93QS95D D118K A136P D139R Q169R N200T S202R 10.8 A & H 46 C. 65 hr 36.72373.8 R210G W260F N283H L288I L294P S295V A30T Y93Q S95D D118K A136PD139R E177S N200T S202R 10.8 A & H 46 C. 65 hr 35.8 2339.7 R210G W260FN283H L288I L294P S295V A30T Y93Q S95D D118K A136P D139R N150T N200TS202R 10.8 A & H 46 C. 65 hr 32.0 2334.4 R210G W260F N283H L288I L294PS295V A30T Y93Q S95D D118K A136P D139R N150S N200T S202R 10.8 A & H 46C. 65 hr 33.8 2281.6 R210G W260F N283H L288I L294P S295V A30T Y93Q S95DD118K A136P D139R N150R N200T S202R 10.8 A & H 46 C. 65 hr 32.0 2219.7R210G W260F N283H L288I L294P S295V A30T Y93Q S95D D118K A136P D139RQ184E N200T S202R 10.8 A & H 46 C. 65 hr 32.7 2331.0 R210G W260F N283HL288I L294P S295V A30T Y93Q S95D D118K A136P D139R Q184K N200T S202R10.8 A & H 46 C. 65 hr 31.4 2150.7 R210G W260F N283H L288I L294P S295VA30T Y93Q S95D D118K A136P D139R R185G N200T S202R 10.8 A & H 46 C. 65hr 36.6 2471.9 R210G W260F N283H L288I L294P S295V A30T Y93Q S95D D118KA136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 20.2 1483.1 E234YW260F N283H L288I L294P S295V A30T Y93Q S95D D118K A136P D139R N200TS202R R210G 10.8 A & H 46 C. 65 hr 30.4 2146.6 A235K W260F N283H L288IL294P S295V A30T Y93Q S95D K116R D118K A136P D139R N200T S202R 10.8 A &H 46 C. 65 hr 29.6 2266.8 R210G W260F N283H L288I L294P S295V A30T Y93QS95D D118K T119R A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 21.51742.8 R210G W260F N283H L288I L294P S295V A30T Y93Q S95D N100H D118KA136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 30.5 2074.7 R210G W260FN283H L288I L294P S295V A30T Y93Q S95D D118K A136P D139R N200T S202RR210G 10.8 A & H 46 C. 65 hr 37.2 2553.3 W260F N273D N283H L288I L294PS295V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46C. 65 hr 34.6 2413.6 W260F N273E N283H L288I L294P S295V Y6H A30T Y93QS95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 35.72497.5 W260F N283H L288I L294P S295V A30T Y93Q S95D D118K A136P D139RN200T S202R R210G 10.8 A & H 46 C. 65 hr 28.0 2016.5 W260F N272M N283HL288I L294P S295V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G10.8 A & H 46 C. 65 hr 36.1 2693.8 W260F N272T N283H L288I L294P S295VA30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65hr 33.9 2510.5 W260F A276W N283H L288I L294P S295V A30T Y93Q S95D D118KA136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 40.3 2695.7 W260FA276D N283H L288I L294P S295V T11K A30T Y93Q S95D D118K A136P D139RN200T S202R R210G 10.8 A & H 46 C. 65 hr 34.6 2250.0 W260F N283H L288IL294P S295V T11R A30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8A & H 46 C. 65 hr 30.7 2269.2 W260F N283H L288I L294P S295V A30T Q60RY93Q S95D D118K A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 35.22401.7 R210G W260F N283H L288I L294P S295V A30T Y93Q S95D S98P D118KA136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 34.1 2485.3 W260FN283H L288I L294P S295V A30T Y93F S95D D118K A136P D139R N200T S202RR210G 10.8 A & H 46 C. 65 hr 31.5 2246.3 W260F N283H L288I L294P S295VA30T Y93Q S95D I114Q D118K A136P D139R N200T S202R 10.8 A & H 46 C. 65hr 33.3 2457.4 R210G W260F N283H L288I L294P S295V A30T Y93Q S95D D118KA136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 36.9 2528.8 W260FN279E N283H L288I L294P S295V A30T Y93Q S95D D118K A136P D139R N200TS202R R210G 10.8 A & H 46 C. 65 hr 30.0 2167.4 W260F T280L N283H L288IL294P S295V A30T Y93Q S95D S98D D118K A136P D139R N200T S202R R210G 10.8A & H 46 C. 65 hr 37.3 2426.6 W260F N283H L288I L294P S295V A30T Y93QS95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 30.02120.6 W260F N283H L288I L294P S295V T296S A30T Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 32.4 2350.7 W260F N283HL288I L294P S295V F298Y A30T Y93Q S95D D118K A136P D139R N200T S202RR210G 10.8 A & H 46 C. 65 hr 33.8 2458.0 N213V W260F N283H L288I L294PS295V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46C. 65 hr 42.4 2944.5 N213D W260F N283H L288I L294P S295V A30T Y93Q S95DD118K A136P D139R K142M N200T S202R 10.8 A & H 46 C. 65 hr 37.6 2858.1R210G W260F N283H L288I L294P S295V A30T Y93Q S95D D118K A136P D139RK142V N200T S202R 10.8 A & H 46 C. 65 hr 37.3 2740.1 R210G W260F N283HL288I L294P S295V Y6F A30T Y93Q S95D D118K A136P D139R N200T S202R R210G10.8 A & H 46 C. 65 hr 34.5 2471.2 W260F N283H L288I L294P S295V Y6WA30T Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65hr 30.8 2239.3 W260F N283H L288I L294P S295V Y13F A30T Y93Q S95D D118KA136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 34.3 2524.5 W260FN283H L288I L294P S295V A30T Y93Q S95D D118K A136P D139R Y174F N200TS202R 10.8 A & H 46 C. 65 hr 34.8 2344.0 R210G W260F N283H L288I L294PS295V A30T Y93Q S95D D118K A136P D139R Y174W N200T S202R 10.8 A & H 46C. 65 hr 32.6 2249.1 R210G W260F N283H L288I L294P S295V A30T T37R Y93QS95D D118K A136P D139R Q184K N200T S202R 10.8 A & H 46 C. 65 hr 23.11737.1 R210G W260F L288I L294P S295V A30T T37R Y93Q S95D N100H D118KA136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 20.4 1483.1 R210G W260FL288I L294P S295V A30T T37R Y93Q S95D S98P D118K A136P D139R N200T S202R10.8 A & H 46 C. 65 hr 25.5 1742.6 R210G W260F L288I L294P S295V A30TT37R Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65hr 23.6 1711.4 N213V W260F L288I L294P S295V A1G A30T T37R Y93Q S95DD118K A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 31.1 2072.8 R210GW260F L288I L294P S295V A1V A30T T37R Y93Q S95D D118K A136P D139R N200TS202R 10.8 A & H 46 C. 65 hr 30.7 1983.3 R210G W260F L288I L294P S295VA30T T37R Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C.65 hr 36.7 2364.6 Q243K W260F L288I L294P S295V A30T T37R K63R Y93Q S95DD118K A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 22.2 1605.4 R210GW260F L288I L294P S295V S3P A30T T37R Y93Q S95D D118K A136P D139R N200TS202R 10.8 A & H 46 C. 65 hr 27.0 1856.8 R210G W260F L288I L294P S295VS8T A30T T37R Y93Q S95D D118K A136P D139R N200T S202R 10.8 A & H 46 C.65 hr 27.9 1938.2 R210G W260F L288I L294P S295V A30T T37R E77T Y93Q S95DD118K A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 28.0 1845.2 R210GW260F L288I L294P S295V A30T T37R G47S Y93Q S95D D118K A136P D139R N200TS202R 10.8 A & H 46 C. 65 hr 22.9 1670.4 R210G W260F L288I L294P S295VA30T T37R H80K Y93Q S95D D118K A136P D139R N200T S202R 10.8 A & H 46 C.65 hr 32.9 1997.6 R210G W260F L288I L294P S295V A30T T37R Y93Q S95DD118K S131T A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 24.1 1569.1R210G W260F L288I L294P S295V A30T T37R Y93Q S95D D118K A136P D139RN200T S202R R210G 10.8 A & H 46 C. 65 hr 35.4 2257.6 W260F A276E L288IL294P S295V A30T T37R A83S Y93Q S95D D118K A136P D139R N200T S202R 10.8A & H 46 C. 65 hr 29.1 1818.8 R210G W260F L288I L294P S295V A30T T37RE77N Y93Q S95D D118K A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 29.92007.4 R210G W260F L288I L294P S295V A30T T37R G47K Y93Q S95D D118KA136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 23.7 1631.2 R210G W260FL288I L294P S295V A30T T37R H80R Y93Q S95D D118K A136P D139R N200T S202R10.8 A & H 46 C. 65 hr 33.6 2189.4 R210G W260F L288I L294P S295V A30TT37R Y93Q S95D S111K D118K A136P D139R N200T S202R 10.8 A & H 46 C. 65hr 33.1 1943.1 R210G W260F L288I L294P S295V A30T T37R D65E Y93Q S95DD118K A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 22.8 1654.2 R210GW260F L288I L294P S295V A30T T37R N45G Y93Q S95D D118K A136P D139R N200TS202R 10.8 A & H 46 C. 65 hr 26.1 1799.7 R210G W260F L288I L294P S295VN18V A30T T37R Y93Q S95D D118K A136P D139R N200T S202R 10.8 A & H 46 C.65 hr 31.3 1990.7 R210G W260F L288I L294P S295V N18R A30T T37R Y93Q S95DD118K A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 21.9 1599.8 R210GW260F L288I L294P S295V A30T T37R N71S Y93Q S95D D118K A136P D139R N200TS202R 10.8 A & H 46 C. 65 hr 30.7 2043.5 R210G W260F L288I L294P S295VA30T T37R Y93Q S95D D118K A136P D139R N180R N200T S202R 10.8 A & H 46 C.65 hr 30.7 2062.9 R210G W260F L288I L294P S295V A30T T37R Y93Q S95DD118K A136P D139R Q169R N200T S202R 10.8 A & H 46 C. 65 hr 27.4 1828.2R210G W260F L288I L294P S295V A30T T37R Y93Q S95D D118K A136P D139RE177Y N200T S202R 10.8 A & H 46 C. 65 hr 27.1 1804.2 R210G W260F L288IL294P S295V A30T T37R Y93Q S95D D118K A136P D139R N150T N200T S202R 10.8A & H 46 C. 65 hr 29.2 1924.3 R210G W260F L288I L294P S295V A30T T37RY93Q S95D D118K A136P D139R N150S N200T S202R 10.8 A & H 46 C. 65 hr31.4 2075.1 R210G W260F L288I L294P S295V A30T T37R Y93Q S95D D118KA136P D139R N150R N200T S202R 10.8 A & H 46 C. 65 hr 29.6 1880.4 R210GW260F L288I L294P S295V A30T T37R Y93Q S95D D118K A136P D139R Q184EN200T S202R 10.8 A & H 46 C. 65 hr 33.7 1974.6 R210G W260F L288I L294PS295V A30T T37R Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H46 C. 65 hr 25.3 1789.8 E234Y W260F L288I L294P S295V A30T T37R Y93QS95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 23.71663.9 A235R W260F L288I L294P S295V A30T T37R Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 23.7 1747.9 A235K W260FL288I L294P S295V A30T T37R Y93Q S95D K116R D118K A136P D139R N200TS202R 10.8 A & H 46 C. 65 hr 23.1 1664.0 R210G W260F L288I L294P S295VA30T T37R Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C.65 hr 38.4 2453.7 W260F N279D L288I L294P S295V A30T T37R Y93Q S95DD118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 44.7 2929.8W260F N279E L288I L294P S295V A30T T37R Y93Q S95D D118K A136P D139RN200T S202R R210G 10.8 A & H 46 C. 65 hr 33.5 2020.4 W260F N273E L288IL294P S295V Y6H A30T T37R Y93Q S95D D118K A136P D139R N200T S202R 10.8 A& H 46 C. 65 hr 21.5 1647.8 R210G W260F L288I L294P S295V Y6M A30T T37RY93Q S95D D118K A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 23.21704.6 R210G W260F L288I L294P S295V A30T T37R Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 23.0 1633.3 W260F N272ML288I L294P S295V A30T T37R Y93Q S95D D118K A136P D139R N200T S202RR210G 10.8 A & H 46 C. 65 hr 36.6 2155.6 W260F N272T L288I L294P S295VA30T T37R Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C.65 hr 38.8 2351.7 W260F N283W L288I L294P S295V A30T T37R Y93Q S95DD118K A136P D139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 25.4 1786.1W260F A276W L288I L294P S295V A30T T37R Y93Q S95D D118K A136P D139RN200T S202R R210G 10.8 A & H 46 C. 65 hr 36.5 2274.5 W260F A276D L288IL294P S295V A30T T37R Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8A & H 46 C. 65 hr 29.5 1898.1 W260F T280L L288I L294P S295V T11K A30TT37R Y93Q S95D D118K A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 23.71672.6 R210G W260F L288I L294P S295V T11R A30T T37R Y93Q S95D D118KA136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 22.1 1610.5 R210G W260FL288I L294P S295V A30T T37R D57N Y93Q S95D D118K A136P D139R N200T S202R10.8 A & H 46 C. 65 hr 28.3 1886.8 R210G W260F L288I L294P S295V A30TT37R Q60R Y93Q S95D D118K A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr38.3 2453.4 R210G W260F L288I L294P S295V A30T T37R Y93Q S95D I114MD118K A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 22.6 1594.1 R210GW260F L288I L294P S295V A30T T37R Y93Q S95D I114Q D118K A136P D139RN200T S202R 10.8 A & H 46 C. 65 hr 27.7 1871.8 R210G W260F L288I L294PS295V A30T T37R Y93Q S95D I114W D118K A136P D139R N200T S202R 10.8 A & H46 C. 65 hr 26.9 1735.6 R210G W260F L288I L294P S295V A30T T37R Y93QS95D S98D D118K A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 28.01827.9 R210G W260F L288I L294P S295V A30T T37R Y93Q S95D D118K A136PD139R N200T S202R R210G 10.8 A & H 46 C. 65 hr 31.2 2035.1 W260F L288IL294P S295V T296S A30T T37R Y93Q S95D D118K A136P D139R N200T S202RR210G 10.8 A & H 46 C. 65 hr 32.6 2113.8 W260F L288I L294P S295V F298YA30T T37R Y93Q S95D D118K A136P D139R N200T S202R R210G 10.8 A & H 46 C.65 hr 31.8 2050.4 N213D W260F L288I L294P S295V A30T T37R Y93Q S95DD118K A136P D139R K142M N200T S202R 10.8 A & H 46 C. 65 hr 34.6 1961.1R210G W260F L288I L294P S295V A30T T37R Y93Q S95D D118K A136P D139RK142V N200T S202R 10.8 A & H 46 C. 65 hr 27.3 1972.1 R210G W260F L288IL294P S295V Y6F A30T T37R Y93Q S95D D118K A136P D139R N200T S202R 10.8 A& H 46 C. 65 hr 27.5 1759.5 R210G W260F L288I L294P S295V Y6W A30T T37RY93Q S95D D118K A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 28.61982.6 R210G W260F L288I L294P S295V Y13F A30T T37R Y93Q S95D D118KA136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 26.6 1754.7 R210G W260FL288I L294P S295V Y13W A30T T37R Y93Q S95D D118K A136P D139R N200T S202R10.8 A & H 46 C. 65 hr 23.9 1621.2 R210G W260F L288I L294P S295V A30TT37R Y93Q S95D D118K A136P D139R Y174F N200T S202R 10.8 A & H 46 C. 65hr 31.0 1993.8 R210G W260F L288I L294P S295V A30T Y32F T37R Y93Q S95DD118K A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr 32.6 1944.6 R210GW260F L288I L294P S295V A30T Y32W T37R Y93Q S95D D118K A136P D139R N200TS202R 10.8 A & H 46 C. 65 hr 28.2 1865.3 R210G W260F L288I L294P S295VA30T Y93Q S95D D118K A136P D139R E177Y S202R R210G 10.8 A & H 46 C. 65hr 26.1 2035.6 W260F A276E L288I L294P S295V A1G A30T Y93Q S95D D118KA136P D139R S202R R210G W260F 10.8 A & H 46 C. 65 hr 24.1 2002.8 A276EL288I L294P S295V A30T Y93Q S95D D118K A136P D139R S202R R210G Q243K10.8 A & H 46 C. 65 hr 33.3 2598.9 W260F A276E L288I L294P S295V A30TY93Q S95D D118K A136P D139R S202R R210G Q243H 10.8 A & H 46 C. 65 hr23.0 1923.1 W260F A276E L288I L294P S295V S8T A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 46 C. 65 hr 24.6 2010.3 A276E L288IL294P S295V A30T H80K Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H46 C. 65 hr 23.7 1929.8 W260F A276E L288I L294P S295V A30T A83S Y93QS95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 21.0 1817.2W260F A276E L288I L294P S295V A30T H80R Y93Q S95D D118K A136P D139RS202R R210G 10.8 A & H 46 C. 65 hr 28.0 2324.8 W260F A276E L288I L294PS295V A30T E41V Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C.65 hr 29.3 2383.7 W260F A276E L288I L294P S295V A30T Y93Q S95D S111AD118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 22.0 1847.5 W260FA276E L288I L294P S295V A30T Y93Q S95D S111K D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 25.1 2057.5 W260F A276E L288I L294P S295VA30T T37R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr27.4 2139.1 W260F A276E L288I L294P S295V A30T R70K Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 30.8 2473.1 W260F A276EL288I L294P S295V A30T N45G Y93Q S95D D118K A136P D139R S202R R210G 10.8A & H 46 C. 65 hr 25.9 2058.6 W260F A276E L288I L294P S295V N18V A30TY93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 28.12194.3 W260F A276E L288I L294P S295V A30T N71S Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 46 C. 65 hr 24.1 2086.3 W260F A276E L288IL294P S295V A30T Y93Q S95D D118K A136P D139R N180R S202R R210G 10.8 A &H 46 C. 65 hr 24.5 2119.1 W260F A276E L288I L294P S295V A30T Y93Q S95DD118K A136P D139R Q169R S202R R210G 10.8 A & H 46 C. 65 hr 29.3 2336.3W260F A276E L288I L294P S295V A30T Y93Q S95D D118K A136P D139R E177SS202R R210G 10.8 A & H 46 C. 65 hr 26.4 2145.2 W260F A276E L288I L294PS295V A30T Y93Q S95D D118K A136P D139R N150S S202R R210G 10.8 A & H 46C. 65 hr 30.1 2433.7 W260F A276E L288I L294P S295V A30T Y93Q S95D D118KA136P D139R Q184E S202R R210G 10.8 A & H 46 C. 65 hr 25.1 1902.6 W260FA276E L288I L294P S295V A30T Y93Q S95D D118K A136P D139R Q184K S202RR210G 10.8 A & H 46 C. 65 hr 22.1 1965.7 W260F A276E L288I L294P S295VA30T Y93Q S95D D118K A136P D139R Q184S S202R R210G 10.8 A & H 46 C. 65hr 24.2 2036.7 W260F A276E L288I L294P S295V A30T Y93Q S95D D118K A136PD139R R185G S202R R210G 10.8 A & H 46 C. 65 hr 32.3 2752.6 W260F A276EL288I L294P S295V A30T Y93Q S95D D118K A136P D139R S202R R210G A235R10.8 A & H 46 C. 65 hr 23.4 2166.2 W260F A276E L288I L294P S295V A30TY93Q S95D D118K A136P D139R S202R R210G A235K 10.8 A & H 46 C. 65 hr23.7 2066.5 W260F A276E L288I L294P S295V A30T Y93Q S95D K116R D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 20.8 1844.9 W260F A276EL288I L294P S295V A30T Y93Q S95D D118K A136P D139R N200T S202R R210G10.8 A & H 46 C. 65 hr 28.1 2233.3 W260F A276E L288I L294P S295V A30TY93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 46 C. 65 hr32.0 2542.7 A276E N283W L288I L294P S295V A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 46 C. 65 hr 35.3 2754.1 A276E N283HL288I L294P S295V A30T Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 46 C. 65 hr 28.9 2349.9 A276E N279E L288I L294P S295V A30TY93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 46 C. 65 hr23.8 1979.7 A276E N279D L288I L294P S295V T11K A30T Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 22.2 1917.1 W260F A276EL288I L294P S295V T11R A30T Y93Q S95D D118K A136P D139R S202R R210G 10.8A & H 46 C. 65 hr 22.4 1913.3 W260F A276E L288I L294P S295V A30T Q60RY93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 27.32195.4 W260F A276E L288I L294P S295V A30T Y93F S95D D118K A136P D139RS202R R210G W260F 10.8 A & H 46 C. 65 hr 20.0 1660.0 A276E L288I L294PS295V A30T Y93Q S95D I114Q D118K A136P D139R S202R R210G 10.8 A & H 46C. 65 hr 24.9 2080.1 W260F A276E L288I L294P S295V A30T Y93Q S95D I114WD118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 22.4 2088.0 W260FA276E L288I L294P S295V A30T Y93Q S95D D118K A136P D139R S202R Q203TR210G 10.8 A & H 46 C. 65 hr 25.2 2078.1 W260F A276E L288I L294P S295VA30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 46 C. 65hr 23.1 2039.5 A276E L288I L294P S295V F298Y A30T Y93Q S95D D118K A136PD139R S202R R210G N213V 10.8 A & H 46 C. 65 hr 20.2 1841.1 W260F A276EL288I L294P S295V A30T Y93Q S95D D118K A136P D139R S202R R210G N213D10.8 A & H 46 C. 65 hr 26.4 2114.7 W260F A276E L288I L294P S295V A30TY93Q S95D D118K A136P D139R K142M S202R R210G 10.8 A & H 46 C. 65 hr27.0 2168.5 W260F A276E L288I L294P S295V A30T Y93Q S95D D118K A136PD139R K142V S202R R210G 10.8 A & H 46 C. 65 hr 20.5 1532.7 W260F A276EL288I L294P S295V A30T Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 46 C. 65 hr 25.7 2105.4 N272T A276E L288I L294P S295V A30TY93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 46 C. 65 hr29.1 2349.3 N273D A276E L288I L294P S295V A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 46 C. 65 hr 29.6 2260.5 N273E A276EL288I L294P S295V A30T Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 46 C. 65 hr 34.6 2693.5 A276E T280L L288I L294P S295V Y6FA30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 46 C. 65hr 21.9 1839.0 A276E L288I L294P S295V Y13W A30T Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 46 C. 65 hr 23.0 1744.4 W260F A276E L288IL294P S295V A30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A &H 46 C. 65 hr 27.2 2191.5 A276E L288I L294P S295V A30T Y93Q S95D D118KA136P D139R Y174F S202R R210G 10.8 A & H 46 C. 65 hr 27.5 2422.3 W260FA276E L288I L294P S295V A30T Y32F Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 34.9 2838.3 W260F A276E L288I L294P S295VA30T Y32W Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr29.7 2472.2 W260F A276E L288I L294P S295V A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 46 C. 65 hr 25.8 2192.0 Y262F A276EL288I L294P S295V A30T Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 46 C. 65 hr 25.1 2188.7 Y262W A276E L288I L294P S295V A30TY93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 46 C. 65 hr25.6 2136.2 A276E Y286F L288I L294P S295V A30T Y93Q S95D D118K A136PD139R S202R R210G W260F 10.8 A & H 46 C. 65 hr 21.7 1909.6 L288I L294PS295V A276E K142R A30T Y93Q S95D D118K A136P D139R S202R R210G W260F10.8 A & H 46 C. 65 hr 24.4 2180.0 L288I L294P S295V A276E K142Q A30TQ60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 20.61861.0 W260F A276D L288I L294P S295V T119R A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 35.9 3168.3 W260F A276DL288I L294P S295V I114W A30T Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 37.9 3280.9 W260F A276D L288I L294P S295VN272T A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C.65 hr 44.0 3877.9 Q243Y W260F A276D L288I L294P S295V A30T Q60R Y93QS95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 42.0 3543.5W260F A276D L288I L294P S295V Q243K A30T Q60R Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 46 C. 65 hr 32.9 2532.5 W260F A276D L288IL294P S295V S3P A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A& H 46 C. 65 hr 33.8 2805.2 W260F A276D L288I L294P S295V T37P A30T Q60RY93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 27.12377.8 W260F A276D L288I L294P S295V G47S A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 29.8 2644.1 W260F A276DL288I L294P S295V S131T A30T Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 34.3 3092.7 W260F A276D L288I L294P S295VA83S A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C.65 hr 33.5 2760.3 W260F A276D L288I L294P S295V E77N A30T Q60R Y93Q S95DD118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 21.0 1998.4 W260FA276D L288I L294P S295V G47K A30T Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 36.0 2984.9 W260F A276D L288I L294P S295VE41V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C.65 hr 39.0 3278.9 W260F A276D L288I L294P S295V S111R A30T Q60R Y93QS95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 28.7 2610.3W260F A276D L288I L294P S295V S111K A30T Q60R Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 46 C. 65 hr 24.2 2374.9 W260F A276D L288IL294P S295V Q35L A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8A & H 46 C. 65 hr 21.9 2191.4 W260F A276D L288I L294P S295V D65E A30TQ60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 35.33174.7 W260F A276D L288I L294P S295V T37R A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 32.7 2889.1 W260F A276DL288I L294P S295V R70K A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G10.8 A & H 46 C. 65 hr 37.1 3138.7 W260F A276D L288I L294P S295V N45GN18V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C.65 hr 49.5 4404.9 W260F A276D L288I L294P S295V A30T Q60R Y93Q S95DD118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 33.5 2960.4 W260FA276D L288I L294P S295V N71S A30T Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 29.9 2660.6 W260F A276D L288I L294P S295VN180R A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C.65 hr 36.0 3135.5 W260F A276D L288I L294P S295V E177S A30T Q60R Y93QS95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 42.9 3456.8W260F A276D L288I L294P S295V E177Y A30T Q60R Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 46 C. 65 hr 37.1 3207.9 W260F A276D L288IL294P S295V N150R A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8A & H 46 C. 65 hr 32.7 2781.0 W260F A276D L288I L294P S295V Q184E A30TQ60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 33.62947.7 W260F A276D L288I L294P S295V Q184K A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 29.6 2711.9 W260F A276DL288I L294P S295V E234Y A30T Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 29.4 2610.7 W260F A276D L288I L294P S295VA235R A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C.65 hr 32.9 2860.0 W260F A276D L288I L294P S295V A235K A30T Q60R Y93QS95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 36.1 3121.0W260F A276D L288I L294P S295V K116R A30T Q60R Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 46 C. 65 hr 36.8 3023.5 W260F A276D L288IL294P S295V N200T A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8A & H 46 C. 65 hr 30.9 2720.4 W260F A276D L288I L294P S295V Y6M A30TQ60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 39.23327.0 W260F A276D L288I L294P S295V N279D A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 24.8 2415.8 W260F A276DL288I L294P S295V T11R A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G10.8 A & H 46 C. 65 hr 35.6 3143.0 W260F A276D L288I L294P S295V S98PA30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr40.0 3251.3 W260F A276D L288I L294P S295V I114M A30T Q60R Y93Q S95DD118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 42.7 3675.1 W260FA276D L288I L294P S295V S98D A30T Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 33.2 2917.9 W260F A276D L288I L294P S295VT296S A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C.65 hr 30.2 2655.1 W260F A276D L288I L294P S295V F298Y A30T Q60R Y93QS95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 32.1 2727.3W260F A276D L288I L294P S295V N213V A30T Q60R Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 46 C. 65 hr 32.0 2711.6 W260F A276D L288IL294P S295V K142V A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8A & H 46 C. 65 hr 30.5 2577.5 W260F A276D L288I L294P S295V D57N A30TQ60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 35.82923.8 W260F A276D L288I L294P S295V N272M A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 45.5 3939.5 W260F N273DA276E L288I L294P S295V A30T Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 40.6 3352.8 W260F A276D L288I L294P S295VN273E A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C.65 hr 43.9 3792.8 W260F A276D L288I L294P S295V T280L A30T Q60R Y93QS95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 32.9 2715.6W260F A276D L288I L294P S295V Y6F A30T Q60R Y93Q S95D D118K A136P D139RS202R R210G 10.8 A & H 46 C. 65 hr 31.4 2638.0 W260F A276D L288I L294PS295V Y6W A30T Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H46 C. 65 hr 40.2 3510.2 W260F A276D L288I L294P S295V Y13F A30T Q60RY93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 31.42746.1 W260F A276D L288I L294P S295V Y13W A30T Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 32.7 2827.8 W260F A276DL288I L294P S295V Y174F A30T Q60R Y93Q S95D D118K A136P D139R S202RR210G 10.8 A & H 46 C. 65 hr 41.1 3502.9 W260F A276D L288I L294P S295VY32F A30T Q60R K63R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H46 C. 65 hr 25.0 2219.9 W260F A276D L288I L294P S295V A30T Q60R Y93QS95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 27.4 2311.4W260F A276D L288I L294P S295V Y6H A30T Y32W Q60R Y93Q S95D D118K A136PD139R S202R R210G 10.8 A & H 46 C. 65 hr 26.1 2770.3 W260F N272T L288IL294P S295V A30T Y32W Q60R Y93Q S95D I114M D118K A136P D139R S202R 10.8A & H 46 C. 65 hr 20.8 2182.2 R210G W260F L288I L294P S295V A1G A30TY32W Q60R Y93Q S95D D118K A136P D139R S202R 10.8 A & H 46 C. 65 hr 29.52676.0 R210G W260F L288I L294P S295V S8T A30T Y32W Q60R Y93Q S95D D118KA136P D139R S202R 10.8 A & H 46 C. 65 hr 26.9 2603.0 R210G W260F L288IL294P S295V A30T Y32W Q60R E77T Y93Q S95D D118K A136P D139R S202R 10.8 A& H 46 C. 65 hr 25.1 2452.8 R210G W260F L288I L294P S295V A30T Y32W Q60RH80K Y93Q S95D D118K A136P D139R S202R 10.8 A & H 46 C. 65 hr 20.82340.4 R210G W260F L288I L294P S295V A30T Y32W Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 30.0 3128.6 W260F A276EL288I L294P S295V A30T Y32W Q60R A83S Y93Q S95D D118K A136P D139R S202R10.8 A & H 46 C. 65 hr 25.1 2573.4 R210G W260F L288I L294P S295V A30TY32W Q60R E77N Y93Q S95D D118K A136P D139R S202R 10.8 A & H 46 C. 65 hr25.3 2671.2 R210G W260F L288I L294P S295V A30T Y32W T37R Q60R Y93Q S95DD118K A136P D139R S202R 10.8 A & H 46 C. 65 hr 30.0 2841.1 R210G W260FL288I L294P S295V A30T Y32W Q60R R70K Y93Q S95D D118K A136P D139R S202R10.8 A & H 46 C. 65 hr 29.3 3021.7 R210G W260F L288I L294P S295V N18VA30T Y32W Q60R Y93Q S95D D118K A136P D139R S202R 10.8 A & H 46 C. 65 hr28.6 2844.1 R210G W260F L288I L294P S295V A30T Y32W Q60R Y93Q S95D D118KA136P D139R Q169R S202R 10.8 A & H 46 C. 65 hr 26.5 2589.2 R210G W260FL288I L294P S295V A30T Y32W Q60R Y93Q S95D D118K A136P D139R N150S S202R10.8 A & H 46 C. 65 hr 27.1 2931.9 R210G W260F L288I L294P S295V A30TY32W Q60R Y93Q S95D D118K A136P D139R N150R S202R 10.8 A & H 46 C. 65 hr21.6 2326.0 R210G W260F L288I L294P S295V A30T Y32W Q60R Y93Q S95D D118KA136P D139R Q184E S202R 10.8 A & H 46 C. 65 hr 22.0 2319.1 R210G W260FL288I L294P S295V A30T Y32W Q60R Y93Q S95D D118K A136P D139R R185G S202R10.8 A & H 46 C. 65 hr 21.5 2280.7 R210G W260F L288I L294P S295V A30TY32W Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr27.6 2847.9 E234Y W260F L288I L294P S295V A30T Y32W Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 20.4 2052.8 A235R W260FL288I L294P S295V A30T Y32W Q60R Y93Q S95D D118K A136P D139R S202R R210G10.8 A & H 46 C. 65 hr 22.6 2465.6 A235K W260F L288I L294P S295V A30TY32W Q60R Y93Q S95D D118K A136P D139R N200T S202R 10.8 A & H 46 C. 65 hr25.2 2566.9 R210G W260F L288I L294P S295V A30T Y32W Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 30.2 2959.5 W260F N279DL288I L294P S295V Y6M A30T Y32W Q60R Y93Q S95D D118K A136P D139R S202R10.8 A & H 46 C. 65 hr 21.9 2249.3 R210G W260F L288I L294P S295V A30TY32W Q60R Y93Q S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr23.6 2429.8 W260F N283W L288I L294P S295V A30T Y32W Q60R Y93Q S95D D118KA136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 32.8 3105.0 W260F N283HL288I L294P S295V A30T Y32W Q60R Y93Q S95D D118K A136P D139R S202R R210G10.8 A & H 46 C. 65 hr 32.3 3099.4 W260F T280L L288I L294P S295V A30TY32W Q60R Y93F S95D D118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr24.1 2534.3 W260F L288I L294P S295V A30T Y32W Q60R Y93Q S95D I114W D118KA136P D139R S202R 10.8 A & H 46 C. 65 hr 20.9 2284.1 R210G W260F L288IL294P S295V A30T Y32W Q60R Y93Q S95D S98D D118K A136P D139R S202R 10.8 A& H 46 C. 65 hr 24.2 2505.5 R210G W260F L288I L294P S295V A30T Y32W Q60RY93Q S95D D118K A136P D139R S202R Q203T 10.8 A & H 46 C. 65 hr 21.42262.9 R210G W260F L288I L294P S295V A30T Y32W Q60R Y93Q S95D D118KA136P D139R K142M S202R 10.8 A & H 46 C. 65 hr 38.3 3633.1 R210G W260FL288I L294P S295V A30T Y32W Q60R Y93Q S95D D118K A136P D139R Y174F S202R10.8 A & H 46 C. 65 hr 29.0 2917.3 R210G W260F L288I L294P S295V A30TY32W K33Q Q60R Y93Q S95D D118K A136P D139R S202R 10.8 A & H 46 C. 65 hr20.6 2261.6 R210G W260F L288I L294P S295V N18V A30T S74K Y93Q S95D D118KA136P D139R N180R S202R 10.8 A & H 46 C. 65 hr 50.6 2992.9 R210G W260FA276D N283H L288I L294P S295V S8T A30T Y93Q S95D D118K A136P D139R N150TS202R R210G 10.8 A & H 46 C. 65 hr 53.7 3146.2 Q243K W260F A276D L288IL294P S295V S8T A30T Y93Q S95D D118K A136P D139R N150T S202R R210G 10.8A & H 46 C. 65 hr 51.7 2965.8 Q243K W260F A276D L288I L294P S295V A30TY93Q S95D D118K A136P D139R P183T N200T R202S 10.8 A & H 46 C. 65 hr51.5 3048.8 R210G W260F D276A N279E L288I L294P S295V A30T Y93Q S95DD118K A136P D139R S202R R205K R210G 10.8 A & H 46 C. 65 hr 45.8 2853.8Q243K W260F A276D L288I L294P S295V A1V A30T Y93Q D118K A136P D139RS202R R210G A257G 10.8 A & H 46 C. 65 hr 62.3 4024.9 W260F A276D L288IL294P S295V A1V A30T Y93Q D118K A136P D139R E177Y S202R R210G G257A 10.8A & H 46 C. 65 hr 48.8 2649.5 W260F A276D L288I L294P S295V A1V Y6H A30TT37P G47T Q60R Y93Q D118K A136P D139R 10.8 A & H 46 C. 65 hr 46.9 2511.9S202R R210G A257G W260F A276D L288I L294P S295V A1V A30T T37P G47T Y93QD118K A136P D139R S202R R210G 10.8 A & H 46 C. 65 hr 42.8 2243.1 A257GW260F A276D L288I L294P S295V A1V A30T T37P G47T Y93Q D118K A136P D139RS202R R210G 10.8 A & H 46 C. 65 hr 41.1 2141.6 G257A W260F A276D L288IL294P S295V A1V A30T Y93Q D118K A136P D139R N150T S202R R210G Q243K 10.8A & H 46 C. 65 hr 37.4 2345.2 G257A W260F A276D L288I L294P S295V A1VA30T Y93Q D118K A136P D139R P183T S202R R205K R210G 10.8 A & H 46 C. 65hr 61.5 4442.8 Q243K G257A W260F A276D L288I L294P S295V A1V A30T Y93QD118K A136P D139R P183T S202R R210G Q243K 10.8 A & H 46 C. 65 hr 60.44294.3 G257A W260F A276D L288I L294P S295V A1V A30T R70K Y93Q D118KA136P D139R P183T S202R R210G 10.8 A & H 46 C. 65 hr 52.8 3531.0 G257AW260F D276A N279D L288I L294P S295V A1V S8T A30T Q60R Y93Q D118K A136PD139R N150T S202R 10.8 A & H 46 C. 65 hr 35.8 2247.7 R210G G257A W260FA276D L288I L294P S295V A1V A30T Y93Q D118K A136P D139R P183T S202RR210G G257A 10.8 A & H 46 C. 65 hr 36.2 2219.6 W260F D276A N279D L288IL294P S295V A1V A30T Y93Q D118K A136P D139R P183T S202R R210G G257A 10.8A & H 46 C. 65 hr 46.8 2967.7 W260F D276A N279E L288I L294P S295V A1VA30T Y93Q D118K A136P D139R N150S S202R R210G R244V 10.8 A & H 46 C. 65hr 40.4 2195.2 G257A W260F A276D L288I L294P S295V A1V A30T Y93Q D118KA136P D139R N150S R176Q S202R 10.8 A & H 46 C. 65 hr 44.9 2482.1 R210GR244V G257A W260F A276D L288I L294P S295V A1V G4D A30T Y93Q D118K A136PD139R S202R R205K R210G 10.8 A & H 46 C. 65 hr 36.2 2130.3 Q243K G257AW260F A276D L288I L294P S295V A1V A30T Y93Q D118K A136P D139R S202RR205K R210G Q243K 10.8 A & H 46 C. 65 hr 41.1 2431.5 G257A W260F A276DL288I L294P S295V A1V A30T Y93Q D118K A136P D139R P183T S202R R210GG257A 10.8 A & H 46 C. 65 hr 43.1 2678.2 W260F A276D L288I L294P S295VA30T Y93Q S95D D118K A136P D139R S202R R210G W260F 10.8 A & H 46 C. 65hr 35.0 2814.1 A276D L288I L294P S295V A30T Y93Q S95D S98P D118K A136PD139R N180R S202R R210G 10.8 A & H 46 C. 65 hr 49.7 2915.3 W260F A276DN283H L288I L294P S295V A30T Y93Q S95D D118K A136P D139R S202R R210GQ243K 10.8 A & H 46 C. 65 hr 51.9 2985.8 W260F A276D L288I L294P S295VS8P A30T Y93Q S95D D118K A136P D139R N150T S202R R210G 10.8 A & H 46 C.65 hr 57.2 3506.0 Q243K W260F A276D L288I L294P S295V A30T R70K Y93QS95D D118K A136P D139R P183T S202R R210G 10.8 A & H 46 C. 65 hr 51.02998.2 W260F D276A N279E L288I L294P S295V A30T Y93Q S95D D118K A136PD139R N150S R176Q S202R 10.8 A & H 46 C. 65 hr 53.1 2975.6 R210G R244VW260F A276D L288I L294P S295V A30T Y93Q S95D D118K A136P D139R P183TS202R R205K 10.8 A & H 46 C. 65 hr 48.7 3099.0 R210G Q243K W260F A276DL288I L294P S295V A30T Y93Q S95D D118K A136P D139R P183T S202R R205K10.8 A & H 46 C. 65 hr 48.6 3092.3 R210G W260F A276D L288I L294P S295VA1V S8R A30T Y93Q D118K A136P D139R S202R R210G G257A 10.8 A & H 42 C.65 hr 34.8 2469.2 W260F A276D L288I L294P S295V A1V S8R A30T N45S Y93QD118K A136P D139R S202R R210G 10.8 A & H 42 C. 65 hr 30.6 2349.3 G257AW260F A276D L288I L294P S295V A1V A30T Y93Q A97E D118K E133Q A136P D139RS202R R210G 10.8 A & H 42 C. 65 hr 34.5 2465.4 G257A W260F A276D L288IL294P S295V A1V A30T E41N Y93Q D118K E133Q A136P D139R S202R R210G 10.8A & H 42 C. 65 hr 34.7 2466.4 G257A W260F A276D L288I L294P S295V A1VA30T E41N R70Q Y93Q A97E D118K A136P D139R S202R 10.8 A & H 42 C. 65 hr41.6 2764.4 R210G G257A W260F A276D L288I L294P S295V A1V A30T Y93QD118K E133Q A136P D139R S202R R210G 10.8 A & H 42 C. 65 hr 33.2 2423.1G257A W260F A276D L288I L294P S295V A1V A30T E41N Y93Q A97E D118K E133QA136P D139R S202R 10.8 A & H 42 C. 65 hr 36.5 2503.6 R210G G257A W260FA276D L288I L294P S295V A1V A30T Y93Q A97E D118K A136P D139R S202R R210GG257A 10.8 A & H 42 C. 65 hr 41.1 2512.9 W260F A276D L288I L294P S295VA1V A30T E41N Y93Q A97E D118K A136P D139R S202R R210G 10.8 A & H 42 C.65 hr 36.1 2469.2 G257A W260F A276D L288I L294P S295V A1V N2E A30T Y93QA97E D118K E133Q A136P D139R S202R 10.8 A & H 42 C. 65 hr 37.8 2651.9R210G G257A W260F A276D L288I L294P S295V A1V N2E A30T E41N Y93Q A97ED118K E133Q A136P D139R 10.8 A & H 42 C. 65 hr 35.4 2472.3 S202R R210GG257A W260F A276D L288I L294P S295V A1V A30T R70Q Y93Q A97E D118K A136PD139R S202R R210G 10.8 A & H 42 C. 65 hr 38.9 2685.4 G257A W260F A276DL288I L294P S295V A1V A30T R70Q Y93Q A97E D118K E133Q A136P D139R S202R10.8 A & H 42 C. 65 hr 37.2 2651.9 R210G G257A W260F A276D L288I L294PS295V A1V A30T E41N R70Q Y93Q A97E D118K E133Q A136P D139R 10.8 A & H 42C. 65 hr 41.1 2378.8 S202R R210G G257A W260F A276D L288I L294P S295V A1VA30T Y93Q D118K D135V A136P D139R S202R R210G G257A 10.8 A & H 42 C. 65hr 45.1 1834.2 W260F A276D L288I L294P S295V A1V A30T Y93Q D118K A136PD139R P183A S202R R210G G257A 10.8 A & H 42 C. 65 hr 41.7 2809.1 W260FA276D L288I L294P S295V

TABLE 3 Variants of the present invention having an improved half lifeImprovement Factor (HIF) measured as improved stability compared to theparent mannanase (SEQ ID NO: 1) Substitutions introduced in SEQ %Residual ID NO: 1 pH Detergent Temperature Time Activity HIF G47A G257W9 Model O 40 C. 16 hr 76.9 3.7 G47S A83P 9 Model O 40 C. 16 hr 74.0 4.2G47A G257L 9 Model O 40 C. 16 hr 73.7 3.5 G47A G257A 9 Model O 40 C. 16hr 70.7 3.0 G47S A136P 9 Model O 40 C. 16 hr 69.1 3.5 S3P G47S E77TK116R A136P G257W 9 Model O 40 C. 16 hr 68.9 2.0 G47S S241C 9 Model O 40C. 16 hr 68.2 2.8 G47S K116R G257W 9 Model O 40 C. 16 hr 67.2 2.4 G47AG2575 9 Model O 40 C. 16 hr 63.8 2.7 G47A A83P 9 Model O 40 C. 16 hr61.5 2.6 G47S Y93Q 9 Model O 40 C. 16 hr 60.6 2.7 G47A Y93C 9 Model O 40C. 16 hr 59.8 2.4 G47A A136P 9 Model O 40 C. 16 hr 59.7 2.4 G47S S98P 9Model O 40 C. 16 hr 58.9 2.5 G47S V82I 9 Model O 40 C. 16 hr 58.8 2.1T37P G47S 9 Model O 40 C. 16 hr 58.7 2.3 G47S G257A 9 Model O 40 C. 16hr 57.7 2.3 G47A D135P 9 Model O 40 C. 16 hr 57.6 2.1 G47A G257Y 9 ModelO 40 C. 16 hr 57.3 2.1 G47S D135P 9 Model O 40 C. 16 hr 56.9 2.2 G47SG257L 9 Model O 40 C. 16 hr 56.4 2.1 S98P G257W 9 Model O 40 C. 16 hr56.0 2.3 G47S K116R 9 Model O 40 C. 16 hr 55.7 2.1 G47S G257F 9 Model O40 C. 16 hr 55.6 2.0 E77T G257F 9 Model O 40 C. 16 hr 55.4 2.1 G47A S98P9 Model O 40 C. 16 hr 55.0 2.0 G47A Y93I 9 Model O 40 C. 16 hr 54.6 1.9T37P G47A 9 Model O 40 C. 16 hr 54.4 1.9 G47S Y93I 9 Model O 40 C. 16 hr54.1 1.9 T37P G257W 9 Model O 40 C. 16 hr 54.0 1.9 G47A Y93Q 9 Model O40 C. 16 hr 53.9 2.0 G47A Y93F 9 Model O 40 C. 16 hr 53.7 2.0 G47S G257S9 Model O 40 C. 16 hr 53.6 2.0 G47A Y93A 9 Model O 40 C. 16 hr 53.5 2.1G47S Y93F 9 Model O 40 C. 16 hr 52.8 1.7 G47A E77T 9 Model O 40 C. 16 hr52.7 1.8 E77T G257W 9 Model O 40 C. 16 hr 52.1 2.1 G47A V82I 9 Model O40 C. 16 hr 52.1 2.0 G47S Y93R 9 Model O 40 C. 16 hr 51.7 2.0 A136PG257W 9 Model O 40 C. 16 hr 51.6 2.0 G47S G257Y 9 Model O 40 C. 16 hr51.3 1.8 G47S G257W 9 Model O 40 C. 16 hr 51.1 1.9 G47A K1166R 9 Model O40 C. 16 hr 50.9 1.8 Y93Q G257W 9 Model O 40 C. 16 hr 50.8 2.2 G47S Y93A9 Model O 40 C. 16 hr 50.0 1.7 T37P G257L 9 Model O 40 C. 16 hr 48.5 1.7G47S Y93C 9 Model O 40 C. 16 hr 48.4 1.7 K116R G257W 9 Model O 40 C. 16hr 46.6 1.8 E77T G257A 9 Model O 40 C. 16 hr 46.3 1.7 G257W P258Q 9Model O 40 C. 16 hr 44.8 1.6 S98P A136P 9 Model O 40 C. 16 hr 44.1 1.5E77T S241C 9 Model O 40 C. 16 hr 43.9 1.4 T37P G257A 9 Model O 40 C. 16hr 43.9 1.5 T37P S2410 9 Model O 40 C. 16 hr 43.6 1.4 G257E P258Q 9Model O 40 C. 16 hr 42.0 1.4 Y93Q A136P 9 Model O 40 C. 16 hr 41.8 1.5E77T A136P 9 Model O 40 C. 16 hr 40.1 1.4 T37P A136P 9 Model O 40 C. 16hr 37.7 1.2 E77T G257Y 9 Model O 40 C. 16 hr 36.6 1.1 T37P G257Y 9 ModelO 40 C. 16 hr 36.5 1.2 E77T Y93R 9 Model O 40 C. 16 hr 36.1 1.2 T37PA83P 9 Model O 40 C. 16 hr 36.1 1.1 E77T K116R 9 Model O 40 C. 16 hr35.8 1.2 G47A S241C 9 Model O 40 C. 16 hr 35.6 1.6 T37P G257S 9 Model O40 C. 16 hr 35.3 1.2 E77T Y93A 9 Model O 40 C. 16 hr 34.6 1.1 E77T Y93I9 Model O 40 C. 16 hr 33.9 1.1 E77T Y93C 9 Model O 40 C. 16 hr 32.6 1.0Y93Q K116R 9 Model O 40 C. 16 hr 32.1 1.1 T37P S98P 9 Model O 40 C. 16hr 31.7 1.0 E77T Y93F 9 Model O 40 C. 16 hr 31.6 1.1 T37P E77T 9 Model O40 C. 16 hr 31.1 1.0 S98P K116R 9 Model O 40 C. 16 hr 30.8 1.1 T37P Y93Q9 Model O 40 C. 16 hr 30.0 1.0 T37P Y93C 9 Model O 40 C. 16 hr 30.0 1.0T37P V82I 9 Model O 40 C. 16 hr 29.6 1.0 T37P Y93A 9 Model O 40 C. 16 hr29.3 1.0 E77T V82I 9 Model O 40 C. 24 hr 24.4 1.3 E77T A83P 9 Model O 40C. 24 hr 25.1 1.3 V82I A83P 9 Model O 40 C. 24 hr 44.8 2.2 D135P A136P 9Model O 40 C. 24 hr 31.3 1.6 E77T D135P 9 Model O 40 C. 24 hr 24.2 1.3E77T G257L 9 Model O 40 C. 24 hr 37.3 1.9 V82I K116R 9 Model O 40 C. 24hr 22.3 1.2 V82I D135P 9 Model O 40 C. 24 hr 26.4 1.4 V82I S241C 9 ModelO 40 C. 24 hr 34.6 1.7 V82I G257A 9 Model O 40 C. 24 hr 29.7 1.5 V82IG257F 9 Model O 40 C. 24 hr 37.3 2.0 V82I G257W 9 Model O 40 C. 24 hr43.9 2.3 V82I G257S 9 Model O 40 C. 24 hr 24.4 1.3 V82I G257Y 9 Model O40 C. 24 hr 24.9 1.3 V82I G257L 9 Model O 40 C. 24 hr 37.9 1.8 Y93CS241C 9 Model O 40 C. 24 hr 37.0 1.8 Y93C G257A 9 Model O 40 C. 24 hr28.6 1.4 Y93C G257W 9 Model O 40 C. 24 hr 48.0 2.3 Y93C G257S 9 Model O40 C. 24 hr 21.5 1.2 Y93C G257Y 9 Model O 40 C. 24 hr 21.5 1.2 Y93CG257L 9 Model O 40 C. 24 hr 38.5 1.9 A83P Y93R 9 Model O 40 C. 24 hr26.9 1.4 A83P Y93A 9 Model O 40 C. 24 hr 22.0 1.2 A83P Y93I 9 Model O 40C. 24 hr 24.0 1.2 A83P Y93C 9 Model O 40 C. 24 hr 26.7 1.4 A83P Y93F 9Model O 40 C. 24 hr 25.2 1.3 A83P Y93Q 9 Model O 40 C. 24 hr 27.4 1.4A83P S98P 9 Model O 40 C. 24 hr 32.1 1.6 A83P K116R 9 Model O 40 C. 24hr 23.8 1.3 A83P D135P 9 Model O 40 C. 24 hr 35.2 1.8 A83P A136P 9 ModelO 40 C. 24 hr 24.6 1.3 A83P S241C 9 Model O 40 C. 24 hr 40.7 2.1 A83PG257A 9 Model O 40 C. 24 hr 38.9 1.9 A83P G257F 9 Model O 40 C. 24 hr49.4 2.4 A83P G257W 9 Model O 40 C. 24 hr 50.6 2.7 A83P G257S 9 Model O40 C. 24 hr 34.9 1.8 A83P G257Y 9 Model O 40 C. 24 hr 31.6 1.6 A83PG257L 9 Model O 40 C. 24 hr 47.0 2.3 Y93A D135P 9 Model O 40 C. 24 hr23.5 1.2 Y93A S241C 9 Model O 40 C. 24 hr 29.5 1.5 Y93A G257A 9 Model O40 C. 24 hr 28.8 1.5 Y93A G257S 9 Model O 40 C. 24 hr 21.4 1.2 Y93AG257L 9 Model O 40 C. 24 hr 31.1 1.6 Y93C D135P 9 Model O 40 C. 24 hr26.4 1.4 Y93F D135P 9 Model O 40 C. 24 hr 22.9 1.2 Y93F A136P 9 Model O40 C. 24 hr 25.1 1.3 Y93F G257A 9 Model O 40 C. 24 hr 62.0 3.8 Y93FG257W 9 Model O 40 C. 24 hr 42.9 2.3 Y93F G257Y 9 Model O 40 C. 24 hr24.4 1.3 Y93F G257L 9 Model O 40 C. 24 hr 38.0 1.9 Y93I D135P 9 Model O40 C. 24 hr 23.9 1.3 Y93I A136P 9 Model O 40 C. 24 hr 24.7 1.3 Y93IS241C 9 Model O 40 C. 24 hr 31.5 1.6 Y93I G257A 9 Model O 40 C. 24 hr25.9 1.3 Y93I G257W 9 Model O 40 C. 24 hr 43.2 2.2 Y93I G257S 9 Model O40 C. 24 hr 20.2 1.1 Y93I G257Y 9 Model O 40 C. 24 hr 24.9 1.3 Y93IG257L 9 Model O 40 C. 24 hr 48.7 2.6 Y93Q D135P 9 Model O 40 C. 24 hr25.9 1.3 Y93Q S241C 9 Model O 40 C. 24 hr 33.0 1.6 Y93Q G257A 9 Model O40 C. 24 hr 27.6 1.4 Y93Q G257F 9 Model O 40 C. 24 hr 34.6 1.8 Y93QG257S 9 Model O 40 C. 24 hr 22.2 1.2 G47S G257E 9 Model O 40 C. 24 hr57.9 3.4 V82R G257W 9 Model O 40 C. 24 hr 51.9 2.5 D135P G257F 9 Model O40 C. 24 hr 49.9 2.4 D135P G257W 9 Model O 40 C. 24 hr 48.6 2.3 A136PG257F 9 Model O 40 C. 24 hr 48.3 2.2 D135P G257A 9 Model O 40 C. 24 hr45.5 2.1 Y93Q G257L 9 Model O 40 C. 24 hr 44.2 2.2 D135P G257E 9 Model O40 C. 24 hr 40.7 2.0 A136P G257L 9 Model O 40 C. 24 hr 38.4 1.8 V82RG257E 9 Model O 40 C. 24 hr 37.9 1.8 D135P G257L 9 Model O 40 C. 24 hr37.5 1.7 S98P S241C 9 Model O 40 C. 24 hr 36.9 2.0 G47S P258Q 9 Model O40 C. 24 hr 36.9 1.8 S98P G257F 9 Model O 40 C. 24 hr 35.7 2.0 S98PG257L 9 Model O 40 C. 24 hr 35.6 1.8 V82R G47S 9 Model O 40 C. 24 hr35.5 1.6 K116R G257L 9 Model O 40 C. 24 hr 34.9 1.8 A136P S241C 9 ModelO 40 C. 24 hr 34.5 1.6 Y93R G257E 9 Model O 40 C. 24 hr 34.4 1.7 D135PS241C 9 Model O 40 C. 24 hr 33.5 1.7 Y93R G257L 9 Model O 40 C. 24 hr32.0 1.7 V82I G257E 9 Model O 40 C. 24 hr 31.5 1.6 A136P G257A 9 Model O40 C. 24 hr 30.9 1.5 D135P G257S 9 Model O 40 C. 24 hr 30.5 1.7 Y93RG257A 9 Model O 40 C. 24 hr 30.4 1.5 Y93R G257W 9 Model O 40 C. 24 hr30.3 1.4 Y93R S241C 9 Model O 40 C. 24 hr 30.2 1.5 S98P G257A 9 Model O40 C. 24 hr 29.9 1.5 Y93R G257F 9 Model O 40 C. 24 hr 29.5 1.4 Y93FG257E 9 Model O 40 C. 24 hr 28.7 1.5 V82R Y93R 9 Model O 40 C. 24 hr28.1 1.5 D135P G257Y 9 Model O 40 C. 24 hr 28.1 1.3 K116R G257F 9 ModelO 40 C. 24 hr 28.1 1.2 A136P G257Y 9 Model O 40 C. 24 hr 26.4 1.3 S98PD135P 9 Model O 40 C. 24 hr 26.3 1.5 A136P G257S 9 Model O 40 C. 24 hr26.0 1.3 K116R S241C 9 Model O 40 C. 24 hr 25.5 1.4 K116R D135P 9 ModelO 40 C. 24 hr 24.6 1.3 K116R G257A 9 Model O 40 C. 24 hr 24.3 1.3 V82RY93F 9 Model O 40 C. 24 hr 22.0 1.2 Y93R A136P 9 Model O 40 C. 24 hr21.9 1.2 Y93R D135P 9 Model O 40 C. 24 hr 20.4 1.1 S241C G257A 9 Model O40 C. 24 hr 47.7 2.4 S241C G257F 9 Model O 40 C. 24 hr 28.8 1.5 S241CG257W 9 Model O 40 C. 24 hr 49.2 2.2 S241C G257S 9 Model O 40 C. 24 hr36.4 1.7 S241C G257Y 9 Model O 40 C. 24 hr 27.3 1.4 S241C G257L 9 ModelO 40 C. 24 hr 51.7 2.7 V82R D135P 9 Model O 40 C. 24 hr 36.8 1.8 T37PV82R 9 Model O 40 C. 24 hr 20.3 1.1 G47A V82R 9 Model O 40 C. 24 hr 26.21.4 G47S V82R 9 Model O 40 C. 24 hr 31.6 1.6 E77T V82R 9 Model O 40 C.24 hr 23.3 1.2 V82R Y93A 9 Model O 40 C. 24 hr 25.2 1.3 V82R Y93I 9Model O 40 C. 24 hr 36.2 1.9 V82R Y93C 9 Model O 40 C. 24 hr 26.2 1.3V82R Y93Q 9 Model O 40 C. 24 hr 28.2 1.5 V82R S98P 9 Model O 40 C. 24 hr26.3 1.4 V82R K116R 9 Model O 40 C. 24 hr 20.7 1.2 V82R A136P 9 Model O40 C. 24 hr 33.8 1.6 V82R S241C 9 Model O 40 C. 24 hr 39.0 1.9 V82RG257A 9 Model O 40 C. 24 hr 43.1 2.2 V82R G257F 9 Model O 40 C. 24 hr35.5 1.8 V82R G257S 9 Model O 40 C. 24 hr 21.7 1.2 V82R G257Y 9 Model O40 C. 24 hr 31.6 1.5 V82R G257L 9 Model O 40 C. 24 hr 41.4 2.0

Example 4 Protease Stability of Mannanase Variants

Variants of the present invention and generated as described in Example1 and 2, were tested for protease stability in Model O detergent at pH9.0 and Model A detergent at pH 7.8. Stability test was performed byincubating the variants in detergent for 4 weeks and at a temperature ofeither 37° C., 40° C. or 50° C. (see tables below) and comparing theactivity against a control sample that was stored at −18° C. for thesame duration.

To the Model O detergent and Model A detergents was added a protease asdisclosed in the tables below.

The residual activity was measured by using the PAHBAH reducing sugarmethod, using carob-galactomannan from Megazyme. Substrate was incubatedwith detergent containing the mannanase enzyme for 30 min at 50° C. Theenzymatic hydrolysis reaction was stopped by adding an alkaline reagentcontaining PAHBAH and Bi³⁺, which reacts with reducing sugars for 20minutes. The resulting yellow color is measured by reading the opticaldensity at 405 nm. The residual activity was calculated by taking theratio of Stress response to Un-stress response and expressing in termsof % RA.

TABLE 4 protease stability at pH 9.0 and 37° C. in Model O detergent(see Table 1). The protease used is a variant of SEQ ID NO: 4 with thefollowing modifications: S9E + N42R + N74D + V199I + Q200L + Y203W +S253D + N255W + L256E added in a 0.2% (w/w) concentration. IncubationResidual Sample time activity % Reference (SEQ ID NO: 2) 4 weeks 0 SEQID NO: 2 + S202R + W260F + 4 weeks 69 L288I + L294P + S295V SEQ ID NO:2 + S202R + W260F + 4 weeks 79 L288I + L294P + S295V +A136P SEQ ID NO:2 + Y93Q + A136P + 4 weeks 94 S202R + W260F + L288I + L294P + S295V SEQID NO: 2 + S98P + A136P + 4 weeks 89 S202R + W260F + L288I + L294P +S295V

TABLE 5 protease stability at pH 7.8 at 40° C. and 50° C. in Model Adetergent (see Table 1). The protease used is a variant of 4 with thefollowing modifications: Y161A + R164S + A188P added in a 0.7% (w/w)concentration. Incubation Residual Sample Temperature time activity %Reference (SEQ ID NO: 2) 40° C. 4 weeks 33 SEQ ID NO: 2 + A30T + Y93Q +S95D + D118K + 40° C. 4 weeks 91 A136P + D139R + N200T + S202R + R210G +W260F + N283H + L288I + L294P + S295V Reference (SEQ ID NO: 2) 50° C. 4weeks 15 SEQ ID NO: 2 + A30T + Y93Q + S95D + D118K + 50° C. 4 weeks 83A136P + D139R + N200T + S202R + R210G + W260F + N283H + L288I + L294P +S295V

The invention described and claimed herein is not to be limited in scopeby the specific aspects herein disclosed, since these aspects areintended as illustrations of several aspects of the invention. Anyequivalent aspects are intended to be within the scope of thisinvention. Indeed, various modifications of the invention in addition tothose shown and described herein will become apparent to those skilledin the art from the foregoing description. Such modifications are alsointended to fall within the scope of the appended claims. In the case ofconflict, the present disclosure including definitions will control.

1. An isolated mannanase variant of a parent mannanase, wherein saidvariant comprises at least two substitutions, wherein (a) said firstsubstitution is in an amino acid position selected from the positions260, 288, 294, or 295, and (b) said at least second substitution isselected from any other position in said variant, wherein numbering isaccording to SEQ ID NO: 2, said variant has mannanase activity and hasat least 58%, e.g. at least 60%, e.g., at least 62%, at least 63%, atleast 65%, at least 70%, at least 75%, at least 80%, at least 85%, atleast 90%, at least 95%, at least 96%, at least 97%, at least 98%, or atleast 99%, but less than 100% sequence identity to the maturepolypeptide of SEQ ID NO: 1 or the polypeptide of SEQ ID NO:
 2. 2. Thevariant according to claim 1, wherein said at least second substitutionis in at least one or more positions selected from the positions: 1, 2,3, 4, 5, 6, 8, 11, 13, 14, 18, 30, 32, 33, 34, 35, 37, 41, 45, 47, 57,59, 60, 63, 65, 70, 71, 74, 77, 78, 80, 82, 83, 93, 95, 97, 98, 100,104, 108, 111, 114, 116, 118, 119, 131, 133, 135, 136, 139, 142, 143,150, 169, 172, 174, 176, 177, 180, 183, 184, 185, 196, 200, 202, 203,205, 210, 213, 228, 229, 234, 235, 241, 243, 244, 250, 254, 257, 262,266, 268, 270, 272, 273, 276, 279, 280, 283, 286, 290, 296, and 298,wherein numbering is according to SEQ ID NO:
 2. 3. The variant accordingto claim 2, wherein said one or more positions are selected from thepositions 14, 37, 47, 77, 81, 82, 83, 93, 98, 116, 135, 136, 241, 242,257, and 258 of the polypeptide of SEQ ID NO:
 2. 4. The variant of claim1, wherein said at least two substitutions are selected from the groupof positions: 14+260, 14+288, 14+294, 14+295, 37+260, 37+288, 37+294,37+295, 47+260, 47+288, 47+294, 47+295, 77+260, 77+288, 77+294, 77+295,81+260, 81+288, 81+294, 81+295, 82+260, 82+288, 82+294, 82+295, 83+260,83+288, 83+294, 83+295, 93+260, 93+288, 93+294, 93+295, 98+260, 98+288,98+294, 98+295, 116+260, 116+288, 116+294, 116+295, 135+260, 135+288,135+294, 135+295, 136+260, 136+288, 136+294, 136+295, 241+260, 241+288,241+294, 241+295, 242+260, 242+288, 242+294, 242+295, 257+260, 257+288,257+294, 257+295, 258+260, 258+288, 258+294, 258+295, 260+288, whereinnumbering is according to SEQ ID NO:
 2. 5. The variant of claim 1,wherein said at least second substitution is in one or both of positions93 and 136 of the polypeptide of SEQ ID NO:
 2. 6. The variant of claim1, wherein at least two substitutions are selected from A1G, A1V, N2E,S3P, G4D, F5H, Y6H, Y6M, Y6F, Y6W, Y6H, S8T, S8P, S8R, T11K, T11R, Y13F,D14S, D14K, N18V, N18R, A30T, Y32F, Y32W, K33Q, D34G, Q35L, T37P, E41V,E41N, N45G, G47S, G47A, D57N, G59Q, Q60R, K63R, K63Q, D65E, R70K, N71S,S74K, E77T, E77N, D78G, H80K, V82R, V82I, V82S, A83P, A83S, Y93Q, Y93A,S95D, A97R, S98P, S98D, N100Y, D104A, D104G, E108S, S111A, S111K, S111R,I114Q, I114M, I114W, K116R, D118K, T119R, S131T, E133R, E133Q, D135P,A136P, D139A, D139R, K142M, K142V, K142S, K142R, Q143R, N150T, N150R,N150S, Q169A, Q169R, Q169K, H172R, Y174R, Y174L, Y174W, Y174F, R176Q,E177S, E177Y, N180R, P183T, P183G, Q184E, Q184K, R185G, Y196W, Y196F,N200T, S202R, Q203T, R205K, R210L, R210G, R210M, N213V, N213D, T228S,N229D, E234F, E234Y, A235K, A235R, S241C, Q243K, Q243E, R244K, R244V,A250G, K254Y, G257W, G257E, G257A, G257G, W260F, W260Y, W260L, W260T,Y262F, S266A, D268N, A270D, N272M, N272T, N273E, N273D, A276E, A276W,A276D, N279D, N279E, T280L, N283W, N283H, Y286W, Y286F, L288I, E290A,L294P, L294K, L294I, L294R, L294V, L294H, S295K, S295V, S295P, S295L,S295R, S295A, S295N, S295M, S295I, T296S, and F298Y.
 7. An isolatedmannanase variant of a parent mannannase, wherein the variant comprisesat least two substitutions in any two or more positions corresponding topositions selected from the group of 3, 37, 47, 77, 82, 83, 93, 98, 116,135, 136, 241, 257, and 258, wherein numbering is according to SEQ IDNO: 2, said variant has mannanase activity and has at least 60%, e.g.,at least 62%, at least 63%, at least 65%, at least 70%, at least 75%, atleast 80%, at least 85%, at least 90%, at least 95%, at least 96%, atleast 97%, at least 98%, or at least 99%, but less than 100% sequenceidentity to the mature polypeptide of SEQ ID NO: 1 or the polypeptide ofSEQ ID NO:
 2. 8. The variant according to claim 7, wherein said at leasttwo of the substitutions are selected from the group of: S3P, T37P,G47A, G47S, E77T, V82I, V82R, A83P, Y93Q, Y93C, Y93A, Y93F, Y93I, Y93R,S98P, K116R, D135P, A136P, S241C, G257W, G257E, G257L, G257A, G257S,G257Y, G257F, and P258Q.
 9. (canceled)
 10. (canceled)
 11. (canceled) 12.The variant of claim 1, wherein said variant has an improved stabilitycompared to said parent mannanase.
 13. The variant of claim 1, whereinsaid improved stability is in-detergent stability or thermostability.14. (canceled)
 15. (canceled)
 16. A composition comprising a variant ofclaim
 1. 17. The composition according to claim 16, wherein saidcomposition further comprises an additional enzyme, such as a protease,amylase or lipase.
 18. The composition of claim 16, wherein saidcomposition further comprises a surfactant, a bleaching system, achelating agents, stabilizing agents, hydrotopes, builders, co-builders,bleach activators, polymers and/or fabric-huing agents.
 19. (canceled)20. (canceled)
 21. (canceled)
 22. (canceled)
 23. (canceled) 24.(canceled)
 25. (canceled)
 26. (canceled)
 27. (canceled)
 28. An isolatedpolynucleotide encoding the variant according to claim
 1. 29. A nucleicacid construct comprising the polynucleotide according to claim
 28. 30.An expression vector comprising the polynucleotide according to claim28.
 31. A host cell comprising the polynucleotide according to claim 28.32. A method of producing a mannanase variant, comprising: a.cultivating the host cell according to claim 31 under conditionssuitable for expression of said variant; and b. recovering said variant.33. (canceled)
 34. A method of dishwashing in an automatic dishwashingmachine comprising the steps of adding said composition of claim 16 in adetergent composition compartment in said automatic dishwashing machine,and releasing said composition during a main-wash cycle.
 35. A method oflaundering in an automatic laundering machine comprising the steps ofadding said composition of claim 16 in a detergent compositioncompartment in said automatic laundering machine, and releasing saidcomposition during a main wash cycle.